[{"publisher":"The Company of Biologists","quality_controlled":"1","oa":1,"day":"01","publication":"Journal of Cell Science","year":"2023","doi":"10.1242/jcs.261448","date_published":"2023-09-01T00:00:00Z","date_created":"2023-09-10T22:01:12Z","article_number":"jcs261448","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"apa":"Nagano, M., Aoshima, K., Shimamura, H., Siekhaus, D. E., Toshima, J. Y., & Toshima, J. (2023). Distinct role of TGN-resident clathrin adaptors for Vps21p activation in the TGN-endosome trafficking pathway. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.261448","ama":"Nagano M, Aoshima K, Shimamura H, Siekhaus DE, Toshima JY, Toshima J. Distinct role of TGN-resident clathrin adaptors for Vps21p activation in the TGN-endosome trafficking pathway. Journal of Cell Science. 2023;136(17). doi:10.1242/jcs.261448","short":"M. Nagano, K. Aoshima, H. Shimamura, D.E. Siekhaus, J.Y. Toshima, J. Toshima, Journal of Cell Science 136 (2023).","ieee":"M. Nagano, K. Aoshima, H. Shimamura, D. E. Siekhaus, J. Y. Toshima, and J. Toshima, “Distinct role of TGN-resident clathrin adaptors for Vps21p activation in the TGN-endosome trafficking pathway,” Journal of Cell Science, vol. 136, no. 17. The Company of Biologists, 2023.","mla":"Nagano, Makoto, et al. “Distinct Role of TGN-Resident Clathrin Adaptors for Vps21p Activation in the TGN-Endosome Trafficking Pathway.” Journal of Cell Science, vol. 136, no. 17, jcs261448, The Company of Biologists, 2023, doi:10.1242/jcs.261448.","ista":"Nagano M, Aoshima K, Shimamura H, Siekhaus DE, Toshima JY, Toshima J. 2023. Distinct role of TGN-resident clathrin adaptors for Vps21p activation in the TGN-endosome trafficking pathway. Journal of Cell Science. 136(17), jcs261448.","chicago":"Nagano, Makoto, Kaito Aoshima, Hiroki Shimamura, Daria E Siekhaus, Junko Y. Toshima, and Jiro Toshima. “Distinct Role of TGN-Resident Clathrin Adaptors for Vps21p Activation in the TGN-Endosome Trafficking Pathway.” Journal of Cell Science. The Company of Biologists, 2023. https://doi.org/10.1242/jcs.261448."},"title":"Distinct role of TGN-resident clathrin adaptors for Vps21p activation in the TGN-endosome trafficking pathway","author":[{"full_name":"Nagano, Makoto","last_name":"Nagano","first_name":"Makoto"},{"full_name":"Aoshima, Kaito","last_name":"Aoshima","first_name":"Kaito"},{"first_name":"Hiroki","full_name":"Shimamura, Hiroki","last_name":"Shimamura"},{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus"},{"first_name":"Junko Y.","last_name":"Toshima","full_name":"Toshima, Junko Y."},{"first_name":"Jiro","last_name":"Toshima","full_name":"Toshima, Jiro"}],"article_processing_charge":"No","external_id":{"pmid":["37539494"]},"oa_version":"Preprint","pmid":1,"abstract":[{"text":"Clathrin-mediated vesicle trafficking plays central roles in post-Golgi transport. In yeast (Saccharomyces cerevisiae), the AP-1 complex and GGA adaptors are predicted to generate distinct transport vesicles at the trans-Golgi network (TGN), and the epsin-related proteins Ent3p and Ent5p (collectively Ent3p/5p) act as accessories for these adaptors. Recently, we showed that vesicle transport from the TGN is crucial for yeast Rab5 (Vps21p)-mediated endosome formation, and that Ent3p/5p are crucial for this process, whereas AP-1 and GGA adaptors are dispensable. However, these observations were incompatible with previous studies showing that these adaptors are required for Ent3p/5p recruitment to the TGN, and thus the overall mechanism responsible for regulation of Vps21p activity remains ambiguous. Here, we investigated the functional relationships between clathrin adaptors in post-Golgi-mediated Vps21p activation. We show that AP-1 disruption in the ent3Δ5Δ mutant impaired transport of the Vps21p guanine nucleotide exchange factor Vps9p transport to the Vps21p compartment and severely reduced Vps21p activity. Additionally, GGA adaptors, the phosphatidylinositol-4-kinase Pik1p and Rab11 GTPases Ypt31p and Ypt32p were found to have partially overlapping functions for recruitment of AP-1 and Ent3p/5p to the TGN. These findings suggest a distinct role of clathrin adaptors for Vps21p activation in the TGN–endosome trafficking pathway.","lang":"eng"}],"month":"09","intvolume":" 136","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2023.03.27.534325"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0021-9533"],"eissn":["1477-9137"]},"publication_status":"published","issue":"17","volume":136,"_id":"14316","status":"public","article_type":"original","type":"journal_article","date_updated":"2023-09-20T09:14:15Z","department":[{"_id":"DaSi"}]},{"file_date_updated":"2023-07-31T07:43:00Z","department":[{"_id":"DaSi"}],"ddc":["570"],"date_updated":"2023-12-13T11:37:36Z","status":"public","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"13316","volume":12,"file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_id":"13324","checksum":"2af111a00cf5e3a956f7f0fd13199b15","creator":"dernst","file_size":11980913,"date_updated":"2023-07-31T07:43:00Z","file_name":"2023_eLife_Toshima.pdf","date_created":"2023-07-31T07:43:00Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2050-084X"]},"publication_status":"published","month":"07","intvolume":" 12","scopus_import":"1","pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Although budding yeast has been extensively used as a model organism for studying organelle functions and intracellular vesicle trafficking, whether it possesses an independent endocytic early/sorting compartment that sorts endocytic cargos to the endo-lysosomal pathway or the recycling pathway has long been unclear. The structure and properties of the endocytic early/sorting compartment differ significantly between organisms; in plant cells, the trans-Golgi network (TGN) serves this role, whereas in mammalian cells a separate intracellular structure performs this function. The yeast syntaxin homolog Tlg2p, widely localizing to the TGN and endosomal compartments, is presumed to act as a Q-SNARE for endocytic vesicles, but which compartment is the direct target for endocytic vesicles remained unanswered. Here we demonstrate by high-speed and high-resolution 4D imaging of fluorescently labeled endocytic cargos that the Tlg2p-residing compartment within the TGN functions as the early/sorting compartment. After arriving here, endocytic cargos are recycled to the plasma membrane or transported to the yeast Rab5-residing endosomal compartment through the pathway requiring the clathrin adaptors GGAs. Interestingly, Gga2p predominantly localizes at the Tlg2p-residing compartment, and the deletion of GGAs has little effect on another TGN region where Sec7p is present but suppresses dynamics of the Tlg2-residing early/sorting compartment, indicating that the Tlg2p- and Sec7p-residing regions are discrete entities in the mutant. Thus, the Tlg2p-residing region seems to serve as an early/sorting compartment and function independently of the Sec7p-residing region within the TGN."}],"title":"The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network","author":[{"full_name":"Toshima, Junko Y.","last_name":"Toshima","first_name":"Junko Y."},{"last_name":"Tsukahara","full_name":"Tsukahara, Ayana","first_name":"Ayana"},{"first_name":"Makoto","full_name":"Nagano, Makoto","last_name":"Nagano"},{"last_name":"Tojima","full_name":"Tojima, Takuro","first_name":"Takuro"},{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus"},{"full_name":"Nakano, Akihiko","last_name":"Nakano","first_name":"Akihiko"},{"first_name":"Jiro","last_name":"Toshima","full_name":"Toshima, Jiro"}],"article_processing_charge":"Yes","external_id":{"isi":["001035372800001"],"pmid":["37477116"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Toshima, Junko Y., et al. “The Yeast Endocytic Early/Sorting Compartment Exists as an Independent Sub-Compartment within the Trans-Golgi Network.” ELife, vol. 12, e84850, eLife Sciences Publications, 2023, doi:10.7554/eLife.84850.","ieee":"J. Y. Toshima et al., “The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network,” eLife, vol. 12. eLife Sciences Publications, 2023.","short":"J.Y. Toshima, A. Tsukahara, M. Nagano, T. Tojima, D.E. Siekhaus, A. Nakano, J. Toshima, ELife 12 (2023).","ama":"Toshima JY, Tsukahara A, Nagano M, et al. The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network. eLife. 2023;12. doi:10.7554/eLife.84850","apa":"Toshima, J. Y., Tsukahara, A., Nagano, M., Tojima, T., Siekhaus, D. E., Nakano, A., & Toshima, J. (2023). The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.84850","chicago":"Toshima, Junko Y., Ayana Tsukahara, Makoto Nagano, Takuro Tojima, Daria E Siekhaus, Akihiko Nakano, and Jiro Toshima. “The Yeast Endocytic Early/Sorting Compartment Exists as an Independent Sub-Compartment within the Trans-Golgi Network.” ELife. eLife Sciences Publications, 2023. https://doi.org/10.7554/eLife.84850.","ista":"Toshima JY, Tsukahara A, Nagano M, Tojima T, Siekhaus DE, Nakano A, Toshima J. 2023. The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network. eLife. 12, e84850."},"article_number":"e84850","doi":"10.7554/eLife.84850","date_published":"2023-07-21T00:00:00Z","date_created":"2023-07-30T22:01:02Z","day":"21","publication":"eLife","isi":1,"has_accepted_license":"1","year":"2023","quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"acknowledgement":"This work was supported by JSPS KAKENHI grant #18K062291, and the Takeda Science Foundation to JYT., as well as JSPS KAKENHI grant #19K065710, the Takeda Science Foundation, and Life Science Foundation of Japan to JT."},{"publication":"Frontiers in Oncology","day":"08","year":"2022","has_accepted_license":"1","isi":1,"date_created":"2022-02-01T10:33:50Z","date_published":"2022-02-08T00:00:00Z","doi":"10.3389/fonc.2022.777634","acknowledgement":"We thank M. Sixt, A. Leithner, and J. Alanko for helpful advice and the BioImaging Facility at IST Austria for technical support and assistance. We thank the Siekhaus Lab for the careful review of the manuscript and their input. MR and DS were funded by the NO Forschungs- und Bildungsges.m.b.H. (LS16-021) and IST core funding. MD was funded by Deutsche Forschungsgemeinschaft (DA 1785-1).","oa":1,"quality_controlled":"1","publisher":"Frontiers","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"short":"M. Roblek, J. Bicher, M. van Gogh, A. György, R. Seeböck, B. Szulc, M. Damme, M. Olczak, L. Borsig, D.E. Siekhaus, Frontiers in Oncology 12 (2022).","ieee":"M. Roblek et al., “The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis,” Frontiers in Oncology, vol. 12. Frontiers, 2022.","apa":"Roblek, M., Bicher, J., van Gogh, M., György, A., Seeböck, R., Szulc, B., … Siekhaus, D. E. (2022). The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. Frontiers. https://doi.org/10.3389/fonc.2022.777634","ama":"Roblek M, Bicher J, van Gogh M, et al. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. 2022;12. doi:10.3389/fonc.2022.777634","mla":"Roblek, Marko, et al. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” Frontiers in Oncology, vol. 12, 777634, Frontiers, 2022, doi:10.3389/fonc.2022.777634.","ista":"Roblek M, Bicher J, van Gogh M, György A, Seeböck R, Szulc B, Damme M, Olczak M, Borsig L, Siekhaus DE. 2022. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. 12, 777634.","chicago":"Roblek, Marko, Julia Bicher, Merel van Gogh, Attila György, Rita Seeböck, Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig, and Daria E Siekhaus. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” Frontiers in Oncology. Frontiers, 2022. https://doi.org/10.3389/fonc.2022.777634."},"title":"The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis","external_id":{"isi":["000760618800001"]},"article_processing_charge":"Yes (via OA deal)","author":[{"last_name":"Roblek","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87","first_name":"Marko"},{"id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","full_name":"Bicher, Julia","last_name":"Bicher"},{"last_name":"van Gogh","full_name":"van Gogh, Merel","first_name":"Merel"},{"first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","full_name":"György, Attila","last_name":"György"},{"first_name":"Rita","full_name":"Seeböck, Rita","last_name":"Seeböck"},{"first_name":"Bozena","last_name":"Szulc","full_name":"Szulc, Bozena"},{"full_name":"Damme, Markus","last_name":"Damme","first_name":"Markus"},{"full_name":"Olczak, Mariusz","last_name":"Olczak","first_name":"Mariusz"},{"first_name":"Lubor","full_name":"Borsig, Lubor","last_name":"Borsig"},{"first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus"}],"article_number":"777634","project":[{"grant_number":"LSC16-021 ","name":"Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis","_id":"2637E9C0-B435-11E9-9278-68D0E5697425"}],"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"10751","checksum":"63dfecf30c5bbf9408b3512bd603f78c","success":1,"date_updated":"2022-02-08T13:26:40Z","file_size":6303227,"creator":"cchlebak","date_created":"2022-02-08T13:26:40Z","file_name":"2022_FrontiersOncol_Roblek.pdf"}],"publication_status":"published","publication_identifier":{"issn":["2234-943X"]},"related_material":{"link":[{"description":"News on IST Homepage","relation":"confirmation","url":"https://ist.ac.at/en/news/suppressing-the-spread-of-tumors/"}]},"volume":12,"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"}],"abstract":[{"text":"Solute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in a mouse model. We identified an increased migratory potential in MFSD1-/- tumor cells which was mediated by increased focal adhesion turn-over, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, down-regulation of MFSD1 expression was observed during early steps of tumorigenesis and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread.","lang":"eng"}],"intvolume":" 12","month":"02","scopus_import":"1","ddc":["570"],"date_updated":"2023-08-02T14:05:44Z","file_date_updated":"2022-02-08T13:26:40Z","department":[{"_id":"DaSi"}],"_id":"10712","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original"},{"publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"publication_status":"published","language":[{"iso":"eng"}],"issue":"7","volume":57,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"abstract":[{"text":"Ribosomal defects perturb stem cell differentiation, causing diseases called ribosomopathies. How ribosome levels control stem cell differentiation is not fully known. Here, we discovered three RNA helicases are required for ribosome biogenesis and for Drosophila oogenesis. Loss of these helicases, which we named Aramis, Athos and Porthos, lead to aberrant stabilization of p53, cell cycle arrest and stalled GSC differentiation. Unexpectedly, Aramis is required for efficient translation of a cohort of mRNAs containing a 5’-Terminal-Oligo-Pyrimidine (TOP)-motif, including mRNAs that encode ribosomal proteins and a conserved p53 inhibitor, Novel Nucleolar protein 1 (Non1). The TOP-motif co-regulates the translation of growth-related mRNAs in mammals. As in mammals, the La-related protein co-regulates the translation of TOP-motif containing RNAs during Drosophila oogenesis. Thus, a previously unappreciated TOP-motif in Drosophila responds to reduced ribosome biogenesis to co-regulate the translation of ribosomal proteins and a p53 repressor, thus coupling ribosome biogenesis to GSC differentiation.","lang":"eng"}],"oa_version":"Preprint","scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1101/2021.04.04.438367","open_access":"1"}],"month":"04","intvolume":" 57","date_updated":"2023-08-02T14:07:13Z","department":[{"_id":"DaSi"}],"_id":"10714","article_type":"original","type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"status":"public","isi":1,"year":"2022","day":"11","publication":"Developmental Cell","page":"883-900.e10","date_published":"2022-04-11T00:00:00Z","doi":"10.1016/j.devcel.2022.03.005","date_created":"2022-02-01T13:15:05Z","acknowledgement":"We are grateful to all members of the Rangan and Fuchs labs for their discussion and comments on the manuscript. We also thanks Dr. Sammons, Dr. Marlow, Life Science Editors, for their thoughts and comments the manuscript Additionally, we thank the Bloomington Stock Center, the Vienna Drosophila Resource Center, the BDGP Gene Disruption Project, and Flybase for fly stocks, reagents, and other resources. P.R. is funded by the NIH/NIGMS (R01GM111779-06 and RO1GM135628-01), G.F. is funded by NSF MCB-2047629 and NIH RO3 AI144839, D.E.S. was funded by Marie Curie CIG 334077/IRTIM and the Austrian Science Fund (FWF) grant ASI_FWF01_P29638S, and A.B is funded by NIH R01GM116889 and American Cancer Society RSG-17-197-01-RMC.","publisher":"Elsevier","quality_controlled":"1","oa":1,"citation":{"ama":"Martin ET, Blatt P, Ngyuen E, et al. A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis. Developmental Cell. 2022;57(7):883-900.e10. doi:10.1016/j.devcel.2022.03.005","apa":"Martin, E. T., Blatt, P., Ngyuen, E., Lahr, R., Selvam, S., Yoon, H. A. M., … Rangan, P. (2022). A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2022.03.005","ieee":"E. T. Martin et al., “A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis,” Developmental Cell, vol. 57, no. 7. Elsevier, p. 883–900.e10, 2022.","short":"E.T. Martin, P. Blatt, E. Ngyuen, R. Lahr, S. Selvam, H.A.M. Yoon, T. Pocchiari, S. Emtenani, D.E. Siekhaus, A. Berman, G. Fuchs, P. Rangan, Developmental Cell 57 (2022) 883–900.e10.","mla":"Martin, Elliot T., et al. “A Translation Control Module Coordinates Germline Stem Cell Differentiation with Ribosome Biogenesis during Drosophila Oogenesis.” Developmental Cell, vol. 57, no. 7, Elsevier, 2022, p. 883–900.e10, doi:10.1016/j.devcel.2022.03.005.","ista":"Martin ET, Blatt P, Ngyuen E, Lahr R, Selvam S, Yoon HAM, Pocchiari T, Emtenani S, Siekhaus DE, Berman A, Fuchs G, Rangan P. 2022. A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis. Developmental Cell. 57(7), 883–900.e10.","chicago":"Martin, Elliot T., Patrick Blatt, Elaine Ngyuen, Roni Lahr, Sangeetha Selvam, Hyun Ah M. Yoon, Tyler Pocchiari, et al. “A Translation Control Module Coordinates Germline Stem Cell Differentiation with Ribosome Biogenesis during Drosophila Oogenesis.” Developmental Cell. Elsevier, 2022. https://doi.org/10.1016/j.devcel.2022.03.005."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Elliot T.","last_name":"Martin","full_name":"Martin, Elliot T."},{"last_name":"Blatt","full_name":"Blatt, Patrick","first_name":"Patrick"},{"full_name":"Ngyuen, Elaine","last_name":"Ngyuen","first_name":"Elaine"},{"first_name":"Roni","full_name":"Lahr, Roni","last_name":"Lahr"},{"first_name":"Sangeetha","full_name":"Selvam, Sangeetha","last_name":"Selvam"},{"first_name":"Hyun Ah M.","last_name":"Yoon","full_name":"Yoon, Hyun Ah M."},{"full_name":"Pocchiari, Tyler","last_name":"Pocchiari","first_name":"Tyler"},{"orcid":"0000-0001-6981-6938","full_name":"Emtenani, Shamsi","last_name":"Emtenani","first_name":"Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87"},{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E","last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353"},{"last_name":"Berman","full_name":"Berman, Andrea","first_name":"Andrea"},{"first_name":"Gabriele","full_name":"Fuchs, Gabriele","last_name":"Fuchs"},{"full_name":"Rangan, Prashanth","last_name":"Rangan","first_name":"Prashanth"}],"article_processing_charge":"No","external_id":{"isi":["000789021800005"]},"title":"A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis","project":[{"grant_number":"334077","name":"Investigating the role of transporters in invasive migration through junctions","_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Drosophila TNFa´s Funktion in Immunzellen","grant_number":"P29638"}]},{"intvolume":" 376","month":"04","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2021.04.19.438995"}],"pmid":1,"oa_version":"Preprint","abstract":[{"text":"Cells migrate through crowded microenvironments within tissues during normal development, immune response, and cancer metastasis. Although migration through pores and tracks in the extracellular matrix (ECM) has been well studied, little is known about cellular traversal into confining cell-dense tissues. We find that embryonic tissue invasion by Drosophila macrophages requires division of an epithelial ectodermal cell at the site of entry. Dividing ectodermal cells disassemble ECM attachment formed by integrin-mediated focal adhesions next to mesodermal cells, allowing macrophages to move their nuclei ahead and invade between two immediately adjacent tissues. Invasion efficiency depends on division frequency, but reduction of adhesion strength allows macrophage entry independently of division. This work demonstrates that tissue dynamics can regulate cellular infiltration.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"}],"volume":376,"issue":"6591","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["0036-8075"]},"status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","article_type":"original","_id":"10713","department":[{"_id":"DaSi"}],"date_updated":"2023-08-02T14:06:15Z","oa":1,"publisher":"American Association for the Advancement of Science","quality_controlled":"1","acknowledgement":"We thank J. Friml, C. Guet, T. Hurd, M. Fendrych and members of the laboratory for comments on the manuscript; the Bioimaging Facility of IST Austria for excellent support and T. Lecuit, E. Hafen, R. Levayer and A. Martin for fly strains. This work was supported by a grant from the Austrian Science Fund FWF: Lise Meitner Fellowship M2379-B28 to M.A and D.S., and internal funding from IST Austria to D.S. and EMBL to S.D.R.","date_created":"2022-02-01T11:23:18Z","date_published":"2022-04-22T00:00:00Z","doi":"10.1126/science.abj0425","page":"394-396","publication":"Science","day":"22","year":"2022","isi":1,"project":[{"_id":"264CBBAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"M02379","name":"Modeling epithelial tissue mechanics during cell invasion"}],"title":"Cell division in tissues enables macrophage infiltration","article_processing_charge":"No","external_id":{"pmid":["35446632"],"isi":["000788553700039"]},"author":[{"first_name":"Maria","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","full_name":"Akhmanova, Maria","orcid":"0000-0003-1522-3162","last_name":"Akhmanova"},{"last_name":"Emtenani","orcid":"0000-0001-6981-6938","full_name":"Emtenani, Shamsi","first_name":"Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Daniel","last_name":"Krueger","full_name":"Krueger, Daniel"},{"first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","full_name":"György, Attila","orcid":"0000-0002-1819-198X","last_name":"György"},{"id":"6de81d9d-e2f2-11eb-945a-af8bc2a60b26","first_name":"Mariana","last_name":"Pereira Guarda","full_name":"Pereira Guarda, Mariana"},{"first_name":"Mikhail","full_name":"Vlasov, Mikhail","last_name":"Vlasov"},{"last_name":"Vlasov","full_name":"Vlasov, Fedor","first_name":"Fedor"},{"full_name":"Akopian, Andrei","last_name":"Akopian","first_name":"Andrei"},{"first_name":"Aparna","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","full_name":"Ratheesh, Aparna","last_name":"Ratheesh"},{"full_name":"De Renzis, Stefano","last_name":"De Renzis","first_name":"Stefano"},{"last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Akhmanova, Maria, Shamsi Emtenani, Daniel Krueger, Attila György, Mariana Pereira Guarda, Mikhail Vlasov, Fedor Vlasov, et al. “Cell Division in Tissues Enables Macrophage Infiltration.” Science. American Association for the Advancement of Science, 2022. https://doi.org/10.1126/science.abj0425.","ista":"Akhmanova M, Emtenani S, Krueger D, György A, Pereira Guarda M, Vlasov M, Vlasov F, Akopian A, Ratheesh A, De Renzis S, Siekhaus DE. 2022. Cell division in tissues enables macrophage infiltration. Science. 376(6591), 394–396.","mla":"Akhmanova, Maria, et al. “Cell Division in Tissues Enables Macrophage Infiltration.” Science, vol. 376, no. 6591, American Association for the Advancement of Science, 2022, pp. 394–96, doi:10.1126/science.abj0425.","short":"M. Akhmanova, S. Emtenani, D. Krueger, A. György, M. Pereira Guarda, M. Vlasov, F. Vlasov, A. Akopian, A. Ratheesh, S. De Renzis, D.E. Siekhaus, Science 376 (2022) 394–396.","ieee":"M. Akhmanova et al., “Cell division in tissues enables macrophage infiltration,” Science, vol. 376, no. 6591. American Association for the Advancement of Science, pp. 394–396, 2022.","ama":"Akhmanova M, Emtenani S, Krueger D, et al. Cell division in tissues enables macrophage infiltration. Science. 2022;376(6591):394-396. doi:10.1126/science.abj0425","apa":"Akhmanova, M., Emtenani, S., Krueger, D., György, A., Pereira Guarda, M., Vlasov, M., … Siekhaus, D. E. (2022). Cell division in tissues enables macrophage infiltration. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.abj0425"}},{"project":[{"_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"334077","name":"Investigating the role of transporters in invasive migration through junctions"},{"call_identifier":"FWF","_id":"264CBBAC-B435-11E9-9278-68D0E5697425","grant_number":"M02379","name":"Modeling epithelial tissue mechanics during cell invasion"},{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen"}],"article_number":"e109049","author":[{"full_name":"Emtenani, Shamsi","orcid":"0000-0001-6981-6938","last_name":"Emtenani","id":"49D32318-F248-11E8-B48F-1D18A9856A87","first_name":"Shamsi"},{"full_name":"Martin, Elliot T","last_name":"Martin","first_name":"Elliot T"},{"first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","full_name":"György, Attila","last_name":"György"},{"last_name":"Bicher","full_name":"Bicher, Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"first_name":"Jakob-Wendelin","full_name":"Genger, Jakob-Wendelin","last_name":"Genger"},{"full_name":"Köcher, Thomas","last_name":"Köcher","first_name":"Thomas"},{"last_name":"Akhmanova","orcid":"0000-0003-1522-3162","full_name":"Akhmanova, Maria","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","first_name":"Maria"},{"id":"6de81d9d-e2f2-11eb-945a-af8bc2a60b26","first_name":"Mariana","full_name":"Pereira Guarda, Mariana","last_name":"Pereira Guarda"},{"id":"3047D808-F248-11E8-B48F-1D18A9856A87","first_name":"Marko","full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","last_name":"Roblek"},{"full_name":"Bergthaler, Andreas","last_name":"Bergthaler","first_name":"Andreas"},{"full_name":"Hurd, Thomas R","last_name":"Hurd","first_name":"Thomas R"},{"first_name":"Prashanth","full_name":"Rangan, Prashanth","last_name":"Rangan"},{"first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus"}],"external_id":{"isi":["000771957000001"]},"article_processing_charge":"Yes (via OA deal)","title":"Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila","citation":{"mla":"Emtenani, Shamsi, et al. “Macrophage Mitochondrial Bioenergetics and Tissue Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” The Embo Journal, vol. 41, e109049, Embo Press, 2022, doi:10.15252/embj.2021109049.","ama":"Emtenani S, Martin ET, György A, et al. Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. The Embo Journal. 2022;41. doi:10.15252/embj.2021109049","apa":"Emtenani, S., Martin, E. T., György, A., Bicher, J., Genger, J.-W., Köcher, T., … Siekhaus, D. E. (2022). Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. The Embo Journal. Embo Press. https://doi.org/10.15252/embj.2021109049","short":"S. Emtenani, E.T. Martin, A. György, J. Bicher, J.-W. Genger, T. Köcher, M. Akhmanova, M. Pereira Guarda, M. Roblek, A. Bergthaler, T.R. Hurd, P. Rangan, D.E. Siekhaus, The Embo Journal 41 (2022).","ieee":"S. Emtenani et al., “Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila,” The Embo Journal, vol. 41. Embo Press, 2022.","chicago":"Emtenani, Shamsi, Elliot T Martin, Attila György, Julia Bicher, Jakob-Wendelin Genger, Thomas Köcher, Maria Akhmanova, et al. “Macrophage Mitochondrial Bioenergetics and Tissue Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” The Embo Journal. Embo Press, 2022. https://doi.org/10.15252/embj.2021109049.","ista":"Emtenani S, Martin ET, György A, Bicher J, Genger J-W, Köcher T, Akhmanova M, Pereira Guarda M, Roblek M, Bergthaler A, Hurd TR, Rangan P, Siekhaus DE. 2022. Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. The Embo Journal. 41, e109049."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Embo Press","quality_controlled":"1","oa":1,"acknowledgement":"We thank the DGRC (NIH grant 2P40OD010949-10A1) for plasmids, the BDSC (NIH grant P40OD018537) and the VDRC for fly stocks, FlyBase for essential genomic information, the BDGP in situ database for data (Tomancak et al, 2007), the IST Austria Bioimaging facility for support, the VBC Core Facilities for RNA sequencing and analysis, and C. Guet, C. Navarro, C. Desplan, T. Lecuit, I. Miguel-Aliaga, and Siekhaus group members for comments on the manuscript. The VBCF Metabolomics Facility is funded by the City of Vienna through the Vienna Business Agency. This work was supported by the Marie Curie CIG 334077/IRTIM (DES), Austrian Science Fund (FWF) Lise Meitner Fellowship M2379-B28 (MA and DES), Austrian Science Fund (FWF) grant ASI_FWF01_P29638S (DES), NIH/NIGMS (R01GM111779-06 (PR), RO1GM135628-01 (PR), European Research Council (ERC) grant no. 677006 “CMIL” (AB), and Natural Sciences and Engineering Research Council of Canada\r\n(RGPIN-2019-06766) (TRH). ","date_published":"2022-03-23T00:00:00Z","doi":"10.15252/embj.2021109049","date_created":"2022-03-24T13:23:09Z","isi":1,"has_accepted_license":"1","year":"2022","day":"23","publication":"The Embo Journal","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","_id":"10918","file_date_updated":"2022-03-24T13:22:41Z","department":[{"_id":"DaSi"},{"_id":"LoSw"}],"date_updated":"2023-08-03T06:13:14Z","ddc":["570"],"scopus_import":"1","month":"03","intvolume":" 41","abstract":[{"lang":"eng","text":"Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors."}],"acknowledged_ssus":[{"_id":"Bio"}],"oa_version":"Published Version","volume":41,"ec_funded":1,"publication_identifier":{"eissn":["1460-2075"]},"publication_status":"published","file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"10919","checksum":"dba48580fe0fefaa4c63078d1d2a35df","creator":"siekhaus","date_updated":"2022-03-24T13:22:41Z","file_size":4344585,"date_created":"2022-03-24T13:22:41Z","file_name":"Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosopila.pdf"}],"language":[{"iso":"eng"}]},{"_id":"12080","type":"journal_article","article_type":"original","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"status":"public","date_updated":"2023-08-03T13:49:07Z","ddc":["570"],"department":[{"_id":"DaSi"}],"file_date_updated":"2023-02-21T23:30:39Z","abstract":[{"text":"Endocytosis is a multistep process involving the sequential recruitment and action of numerous proteins. This process can be divided into two phases: an early phase, in which sites of endocytosis are formed, and a late phase in which clathrin-coated vesicles are formed and internalized into the cytosol, but how these phases link to each other remains unclear. In this study, we demonstrate that anchoring the yeast Eps15-like protein Pan1p to the peroxisome triggers most of the events occurring during the late phase at the peroxisome. At this ectopic location, Pan1p recruits most proteins that function in the late phases—including actin nucleation promoting factors—and then initiates actin polymerization. Pan1p also recruited Prk1 kinase and actin depolymerizing factors, thereby triggering disassembly immediately after actin assembly and inducing dissociation of endocytic proteins from the peroxisome. These observations suggest that Pan1p is a key regulator for initiating, processing, and completing the late phase of endocytosis.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","month":"08","intvolume":" 221","publication_identifier":{"issn":["0021-9525"],"eissn":["1540-8140"]},"publication_status":"published","file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","embargo":"2023-02-20","checksum":"f2e581e66b5cdab9df81b56e850b3eaa","file_id":"12321","file_size":7816875,"date_updated":"2023-02-21T23:30:39Z","creator":"dernst","file_name":"2022_JCB_Enshoji.pdf","date_created":"2023-01-20T09:32:53Z"}],"language":[{"iso":"eng"}],"volume":221,"issue":"10","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","article_number":"e202112138","citation":{"ista":"Enshoji M, Miyano Y, Yoshida N, Nagano M, Watanabe M, Kunihiro M, Siekhaus DE, Toshima JY, Toshima J. 2022. Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway. Journal of Cell Biology. 221(10), e202112138.","chicago":"Enshoji, Mariko, Yoshiko Miyano, Nao Yoshida, Makoto Nagano, Minami Watanabe, Mayumi Kunihiro, Daria E Siekhaus, Junko Y. Toshima, and Jiro Toshima. “Eps15/Pan1p Is a Master Regulator of the Late Stages of the Endocytic Pathway.” Journal of Cell Biology. Rockefeller University Press, 2022. https://doi.org/10.1083/jcb.202112138.","ieee":"M. Enshoji et al., “Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway,” Journal of Cell Biology, vol. 221, no. 10. Rockefeller University Press, 2022.","short":"M. Enshoji, Y. Miyano, N. Yoshida, M. Nagano, M. Watanabe, M. Kunihiro, D.E. Siekhaus, J.Y. Toshima, J. Toshima, Journal of Cell Biology 221 (2022).","ama":"Enshoji M, Miyano Y, Yoshida N, et al. Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway. Journal of Cell Biology. 2022;221(10). doi:10.1083/jcb.202112138","apa":"Enshoji, M., Miyano, Y., Yoshida, N., Nagano, M., Watanabe, M., Kunihiro, M., … Toshima, J. (2022). Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.202112138","mla":"Enshoji, Mariko, et al. “Eps15/Pan1p Is a Master Regulator of the Late Stages of the Endocytic Pathway.” Journal of Cell Biology, vol. 221, no. 10, e202112138, Rockefeller University Press, 2022, doi:10.1083/jcb.202112138."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Mariko","full_name":"Enshoji, Mariko","last_name":"Enshoji"},{"last_name":"Miyano","full_name":"Miyano, Yoshiko","first_name":"Yoshiko"},{"last_name":"Yoshida","full_name":"Yoshida, Nao","first_name":"Nao"},{"full_name":"Nagano, Makoto","last_name":"Nagano","first_name":"Makoto"},{"full_name":"Watanabe, Minami","last_name":"Watanabe","first_name":"Minami"},{"full_name":"Kunihiro, Mayumi","last_name":"Kunihiro","first_name":"Mayumi"},{"last_name":"Siekhaus","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E","first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Junko Y.","last_name":"Toshima","full_name":"Toshima, Junko Y."},{"last_name":"Toshima","full_name":"Toshima, Jiro","first_name":"Jiro"}],"article_processing_charge":"No","external_id":{"isi":["000932770500001"],"pmid":["35984332"]},"title":"Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway","acknowledgement":"This work was supported by JSPS KAKENHI GRANT #18K062291, and the Takeda Science Foundation to J.Y. Toshima, as well as JSPS KAKENHI GRANT #19K065710, the Uehara Memorial Foundation, and Life Science Foundation of JAPAN to J. Toshima.","publisher":"Rockefeller University Press","quality_controlled":"1","oa":1,"isi":1,"has_accepted_license":"1","year":"2022","day":"19","publication":"Journal of Cell Biology","doi":"10.1083/jcb.202112138","date_published":"2022-08-19T00:00:00Z","date_created":"2022-09-11T22:01:54Z"},{"oa":1,"publisher":"Public Library of Science","quality_controlled":"1","acknowledgement":"We thank the following for their contributions: Plasmids were supplied by the Drosophila Genomics Resource Center (NIH 2P40OD010949-10A1); fly stocks were provided by K. Brueckner, B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center (NIH P40OD018537) and the Vienna Drosophila Resource Center, FlyBase for essential genomic information, and the BDGP in situ database for data. For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH and is maintained at the University of Iowa, as well as J. Zeitlinger for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria for technical support and assistance with microscopy and FACS analysis. We thank C. P. Heisenberg, P. Martin, M. Sixt, and Siekhaus group members for discussions and T. Hurd, A. Ratheesh, and P. Rangan for comments on the manuscript.","date_created":"2022-01-12T10:18:17Z","doi":"10.1371/journal.pbio.3001494","date_published":"2022-01-06T00:00:00Z","page":"e3001494","publication":"PLoS Biology","day":"06","year":"2022","has_accepted_license":"1","isi":1,"project":[{"grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen","call_identifier":"FWF","_id":"253B6E48-B435-11E9-9278-68D0E5697425"},{"_id":"26199CA4-B435-11E9-9278-68D0E5697425","grant_number":"24800","name":"Tissue barrier penetration is crucial for immunity and metastasis"},{"name":"Investigating the role of transporters in invasive migration through junctions","grant_number":"334077","_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"title":"Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila","article_processing_charge":"No","external_id":{"pmid":["34990456"],"isi":["000971223700001"]},"author":[{"full_name":"Belyaeva, Vera","last_name":"Belyaeva","first_name":"Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","last_name":"Wachner","full_name":"Wachner, Stephanie"},{"last_name":"György","orcid":"0000-0002-1819-198X","full_name":"György, Attila","first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87","last_name":"Emtenani","full_name":"Emtenani, Shamsi","orcid":"0000-0001-6981-6938"},{"first_name":"Igor","id":"4B60654C-F248-11E8-B48F-1D18A9856A87","last_name":"Gridchyn","full_name":"Gridchyn, Igor","orcid":"0000-0002-1807-1929"},{"full_name":"Akhmanova, Maria","orcid":"0000-0003-1522-3162","last_name":"Akhmanova","first_name":"Maria","id":"3425EC26-F248-11E8-B48F-1D18A9856A87"},{"first_name":"M","last_name":"Linder","full_name":"Linder, M"},{"id":"3047D808-F248-11E8-B48F-1D18A9856A87","first_name":"Marko","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko","last_name":"Roblek"},{"first_name":"M","last_name":"Sibilia","full_name":"Sibilia, M"},{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Belyaeva, Vera, Stephanie Wachner, Attila György, Shamsi Emtenani, Igor Gridchyn, Maria Akhmanova, M Linder, Marko Roblek, M Sibilia, and Daria E Siekhaus. “Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” PLoS Biology. Public Library of Science, 2022. https://doi.org/10.1371/journal.pbio.3001494.","ista":"Belyaeva V, Wachner S, György A, Emtenani S, Gridchyn I, Akhmanova M, Linder M, Roblek M, Sibilia M, Siekhaus DE. 2022. Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology. 20(1), e3001494.","mla":"Belyaeva, Vera, et al. “Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” PLoS Biology, vol. 20, no. 1, Public Library of Science, 2022, p. e3001494, doi:10.1371/journal.pbio.3001494.","ieee":"V. Belyaeva et al., “Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila,” PLoS Biology, vol. 20, no. 1. Public Library of Science, p. e3001494, 2022.","short":"V. Belyaeva, S. Wachner, A. György, S. Emtenani, I. Gridchyn, M. Akhmanova, M. Linder, M. Roblek, M. Sibilia, D.E. Siekhaus, PLoS Biology 20 (2022) e3001494.","apa":"Belyaeva, V., Wachner, S., György, A., Emtenani, S., Gridchyn, I., Akhmanova, M., … Siekhaus, D. E. (2022). Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3001494","ama":"Belyaeva V, Wachner S, György A, et al. Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology. 2022;20(1):e3001494. doi:10.1371/journal.pbio.3001494"},"intvolume":" 20","month":"01","scopus_import":"1","pmid":1,"oa_version":"Published Version","abstract":[{"text":"The infiltration of immune cells into tissues underlies the establishment of tissue-resident macrophages and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here, we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio, which are themselves required for invasion. Both the filamin and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous and thus the assembly of cortical actin, which is a critical function since expressing a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect. In vivo imaging shows that Dfos enhances the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the properties of the macrophage nucleus from affecting tissue entry. We thus identify strengthening the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues. ","lang":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"ec_funded":1,"volume":20,"issue":"1","related_material":{"record":[{"relation":"earlier_version","id":"8557","status":"public"},{"id":"11193","status":"public","relation":"dissertation_contains"}],"link":[{"relation":"earlier_version","url":"https://www.biorxiv.org/content/10.1101/2020.09.18.301481"},{"relation":"press_release","url":"https://ista.ac.at/en/news/resisting-the-pressure/","description":"News on the ISTA Website"}]},"language":[{"iso":"eng"}],"file":[{"file_name":"2022_PLOSBio_Belyaeva.pdf","date_created":"2022-01-12T13:50:04Z","creator":"cchlebak","file_size":5426932,"date_updated":"2022-01-12T13:50:04Z","success":1,"checksum":"f454212a5522a7818ba4b2892315c478","file_id":"10615","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"publication_status":"published","publication_identifier":{"issn":["1544-9173"],"eissn":["1545-7885"]},"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","_id":"10614","file_date_updated":"2022-01-12T13:50:04Z","department":[{"_id":"DaSi"},{"_id":"JoCs"}],"ddc":["570"],"date_updated":"2024-03-27T23:30:28Z"},{"date_updated":"2023-09-19T10:15:54Z","supervisor":[{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E","last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353"}],"ddc":["570"],"department":[{"_id":"GradSch"},{"_id":"DaSi"}],"file_date_updated":"2023-04-21T22:30:03Z","_id":"11193","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"dissertation","status":"public","publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","embargo":"2023-04-20","checksum":"999ab16884c4522486136ebc5ae8dbff","file_id":"11195","file_size":8820951,"date_updated":"2023-04-21T22:30:03Z","creator":"cchlebak","file_name":"Thesis_Stephanie_Wachner_20200414_formatted.pdf","date_created":"2022-04-20T09:03:57Z"},{"file_id":"11329","checksum":"fd92b1e38d53bdf8b458213882d41383","embargo_to":"open_access","content_type":"application/x-zip-compressed","relation":"source_file","access_level":"closed","file_name":"Thesis_Stephanie_Wachner_20200414.zip","date_created":"2022-04-22T12:41:00Z","file_size":65864612,"date_updated":"2023-04-21T22:30:03Z","creator":"cchlebak"}],"related_material":{"record":[{"relation":"part_of_dissertation","id":"10614","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"544"}]},"abstract":[{"text":"The infiltration of immune cells into tissues underlies the establishment of tissue-resident\r\nmacrophages and responses to infections and tumors. However, the mechanisms immune\r\ncells utilize to collectively migrate through tissue barriers in vivo are not yet well understood.\r\nIn this thesis, I describe two mechanisms that Drosophila immune cells (hemocytes) use to\r\novercome the tissue barrier of the germband in the embryo. One strategy is the strengthening\r\nof the actin cortex through developmentally controlled transcriptional regulation induced by\r\nthe Drosophila proto-oncogene family member Dfos, which I show in Chapter 2. Dfos induces\r\nexpression of the tetraspanin TM4SF and the filamin Cher leading to higher levels of the\r\nactivated formin Dia at the cortex and increased cortical F-actin. This enhanced cortical\r\nstrength allows hemocytes to overcome the physical resistance of the surrounding tissue and\r\ntranslocate their nucleus to move forward. This mechanism affects the speed of migration\r\nwhen hemocytes face a confined environment in vivo.\r\nAnother aspect of the invasion process is the initial step of the leading hemocytes entering\r\nthe tissue, which potentially guides the follower cells. In Chapter 3, I describe a novel\r\nsubpopulation of hemocytes activated by BMP signaling prior to tissue invasion that leads\r\npenetration into the germband. Hemocytes that are deficient in BMP signaling activation\r\nshow impaired persistence at the tissue entry, while their migration speed remains\r\nunaffected.\r\nThis suggests that there might be different mechanisms controlling immune cell migration\r\nwithin the confined environment in vivo, one of these being the general ability to overcome\r\nthe resistance of the surrounding tissue and another affecting the order of hemocytes that\r\ncollectively invade the tissue in a stream of individual cells.\r\nTogether, my findings provide deeper insights into transcriptional changes in immune\r\ncells that enable efficient tissue invasion and pave the way for future studies investigating the\r\nearly colonization of tissues by macrophages in higher organisms. Moreover, they extend the\r\ncurrent view of Drosophila immune cell heterogeneity and point toward a potentially\r\nconserved role for canonical BMP signaling in specifying immune cells that lead the migration\r\nof tissue resident macrophages during embryogenesis.","lang":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"04","citation":{"mla":"Wachner, Stephanie. Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11193.","short":"S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology Austria, 2022.","ieee":"S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells,” Institute of Science and Technology Austria, 2022.","ama":"Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. 2022. doi:10.15479/at:ista:11193","apa":"Wachner, S. (2022). Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11193","chicago":"Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11193.","ista":"Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","author":[{"id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","full_name":"Wachner, Stephanie","last_name":"Wachner"}],"title":"Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells","project":[{"name":"Tissue barrier penetration is crucial for immunity and metastasis","grant_number":"24800","_id":"26199CA4-B435-11E9-9278-68D0E5697425"}],"year":"2022","has_accepted_license":"1","day":"20","page":"170","date_created":"2022-04-20T08:59:07Z","date_published":"2022-04-20T00:00:00Z","doi":"10.15479/at:ista:11193","oa":1,"publisher":"Institute of Science and Technology Austria"},{"scopus_import":"1","month":"04","intvolume":" 17","abstract":[{"text":"Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and are implicated in degenerative disorders, has never been demonstrated in an animal model of disease. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to inspire novel strategies towards a spatio-temporal regulation of tissue repair.","lang":"eng"}],"oa_version":"Published Version","issue":"4","volume":17,"publication_identifier":{"eissn":["15537404"]},"publication_status":"published","file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"file_id":"9369","checksum":"82a74668f863e8dfb22fdd4f845c92ce","file_size":3072764,"date_updated":"2021-05-04T09:05:27Z","creator":"kschuh","file_name":"2021_PLOS_Ingles-Prieto.pdf","date_created":"2021-05-04T09:05:27Z"}],"language":[{"iso":"eng"}],"type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","_id":"9363","file_date_updated":"2021-05-04T09:05:27Z","department":[{"_id":"EM-Fac"},{"_id":"LoSw"},{"_id":"DaSi"}],"date_updated":"2023-08-08T13:17:47Z","ddc":["570"],"quality_controlled":"1","publisher":"Public Library of Science","oa":1,"acknowledgement":"We thank R. Cagan, A. Whitworth and J. Nagpal for fly lines and advice, S. Herlitze for provision of a tissue culture illuminator, and Verian Bader for help with statistical analysis.","page":"e1009479","doi":"10.1371/journal.pgen.1009479","date_published":"2021-04-01T00:00:00Z","date_created":"2021-05-02T22:01:29Z","has_accepted_license":"1","isi":1,"year":"2021","day":"01","publication":"PLoS genetics","author":[{"id":"2A9DB292-F248-11E8-B48F-1D18A9856A87","first_name":"Álvaro","last_name":"Inglés Prieto","full_name":"Inglés Prieto, Álvaro","orcid":"0000-0002-5409-8571"},{"first_name":"Nikolas","last_name":"Furthmann","full_name":"Furthmann, Nikolas"},{"first_name":"Samuel H.","full_name":"Crossman, Samuel H.","last_name":"Crossman"},{"last_name":"Tichy","full_name":"Tichy, Alexandra Madelaine","first_name":"Alexandra Madelaine"},{"first_name":"Nina","full_name":"Hoyer, Nina","last_name":"Hoyer"},{"last_name":"Petersen","full_name":"Petersen, Meike","first_name":"Meike"},{"last_name":"Zheden","full_name":"Zheden, Vanessa","first_name":"Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bicher, Julia","last_name":"Bicher","first_name":"Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Gschaider-Reichhart","full_name":"Gschaider-Reichhart, Eva","orcid":"0000-0002-7218-7738","first_name":"Eva","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","last_name":"György","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","first_name":"Attila"},{"last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E"},{"last_name":"Soba","full_name":"Soba, Peter","first_name":"Peter"},{"full_name":"Winklhofer, Konstanze F.","last_name":"Winklhofer","first_name":"Konstanze F."},{"last_name":"Janovjak","full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","first_name":"Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","external_id":{"isi":["000640606700001"]},"title":"Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease","citation":{"apa":"Inglés Prieto, Á., Furthmann, N., Crossman, S. H., Tichy, A. M., Hoyer, N., Petersen, M., … Janovjak, H. L. (2021). Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1009479","ama":"Inglés Prieto Á, Furthmann N, Crossman SH, et al. Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS genetics. 2021;17(4):e1009479. doi:10.1371/journal.pgen.1009479","ieee":"Á. Inglés Prieto et al., “Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease,” PLoS genetics, vol. 17, no. 4. Public Library of Science, p. e1009479, 2021.","short":"Á. Inglés Prieto, N. Furthmann, S.H. Crossman, A.M. Tichy, N. Hoyer, M. Petersen, V. Zheden, J. Bicher, E. Gschaider-Reichhart, A. György, D.E. Siekhaus, P. Soba, K.F. Winklhofer, H.L. Janovjak, PLoS Genetics 17 (2021) e1009479.","mla":"Inglés Prieto, Álvaro, et al. “Optogenetic Delivery of Trophic Signals in a Genetic Model of Parkinson’s Disease.” PLoS Genetics, vol. 17, no. 4, Public Library of Science, 2021, p. e1009479, doi:10.1371/journal.pgen.1009479.","ista":"Inglés Prieto Á, Furthmann N, Crossman SH, Tichy AM, Hoyer N, Petersen M, Zheden V, Bicher J, Gschaider-Reichhart E, György A, Siekhaus DE, Soba P, Winklhofer KF, Janovjak HL. 2021. Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS genetics. 17(4), e1009479.","chicago":"Inglés Prieto, Álvaro, Nikolas Furthmann, Samuel H. Crossman, Alexandra Madelaine Tichy, Nina Hoyer, Meike Petersen, Vanessa Zheden, et al. “Optogenetic Delivery of Trophic Signals in a Genetic Model of Parkinson’s Disease.” PLoS Genetics. Public Library of Science, 2021. https://doi.org/10.1371/journal.pgen.1009479."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"file":[{"success":1,"checksum":"56cbac80e6891ce750511a30161b7792","file_id":"10539","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2021_Frontiers_Stefanescu.pdf","date_created":"2021-12-13T13:32:37Z","creator":"alisjak","file_size":9245199,"date_updated":"2021-12-13T13:32:37Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2234-943X"]},"publication_status":"published","volume":11,"pmid":1,"oa_version":"Published Version","abstract":[{"text":"TGFβ overexpression is commonly detected in cancer patients and correlates with poor prognosis and metastasis. Cancer progression is often associated with an enhanced recruitment of myeloid-derived cells to the tumor microenvironment. Here we show that functional TGFβ-signaling in myeloid cells is required for metastasis to the lungs and the liver. Myeloid-specific deletion of Tgfbr2 resulted in reduced spontaneous lung metastasis, which was associated with a reduction of proinflammatory cytokines in the metastatic microenvironment. Notably, CD8+ T cell depletion in myeloid-specific Tgfbr2-deficient mice rescued lung metastasis. Myeloid-specific Tgfbr2-deficiency resulted in reduced liver metastasis with an almost complete absence of myeloid cells within metastatic foci. On contrary, an accumulation of Tgfβ-responsive myeloid cells was associated with an increased recruitment of monocytes and granulocytes and higher proinflammatory cytokine levels in control mice. Monocytic cells isolated from metastatic livers of Tgfbr2-deficient mice showed increased polarization towards the M1 phenotype, Tnfα and Il-1β expression, reduced levels of M2 markers and reduced production of chemokines responsible for myeloid-cell recruitment. No significant differences in Tgfβ levels were observed at metastatic sites of any model. These data demonstrate that Tgfβ signaling in monocytic myeloid cells suppresses CD8+ T cell activity during lung metastasis, while these cells actively contribute to tumor growth during liver metastasis. Thus, myeloid cells modulate metastasis through different mechanisms in a tissue-specific manner.","lang":"eng"}],"month":"11","intvolume":" 11","scopus_import":"1","ddc":["610"],"date_updated":"2023-08-17T06:20:32Z","file_date_updated":"2021-12-13T13:32:37Z","department":[{"_id":"DaSi"}],"_id":"10536","status":"public","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"18","publication":"Frontiers in Oncology","isi":1,"has_accepted_license":"1","year":"2021","date_published":"2021-11-18T00:00:00Z","doi":"10.3389/fonc.2021.765151","date_created":"2021-12-12T23:01:27Z","acknowledgement":"The authors acknowledge the assistance of the Laboratory Animal Services Center (LASC) – UZH, Center for Microscopy and Image Analysis, and the Flow Cytometry Center of the University of Zurich.","publisher":"Frontiers","quality_controlled":"1","oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Stefanescu, Cristina, Merel Van Gogh, Marko Roblek, Mathias Heikenwalder, and Lubor Borsig. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” Frontiers in Oncology. Frontiers, 2021. https://doi.org/10.3389/fonc.2021.765151.","ista":"Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. 2021. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. 11, 765151.","mla":"Stefanescu, Cristina, et al. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” Frontiers in Oncology, vol. 11, 765151, Frontiers, 2021, doi:10.3389/fonc.2021.765151.","apa":"Stefanescu, C., Van Gogh, M., Roblek, M., Heikenwalder, M., & Borsig, L. (2021). TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. Frontiers. https://doi.org/10.3389/fonc.2021.765151","ama":"Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. 2021;11. doi:10.3389/fonc.2021.765151","ieee":"C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, and L. Borsig, “TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms,” Frontiers in Oncology, vol. 11. Frontiers, 2021.","short":"C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, L. Borsig, Frontiers in Oncology 11 (2021)."},"title":"TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms","author":[{"last_name":"Stefanescu","full_name":"Stefanescu, Cristina","first_name":"Cristina"},{"full_name":"Van Gogh, Merel","last_name":"Van Gogh","first_name":"Merel"},{"first_name":"Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87","full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","last_name":"Roblek"},{"last_name":"Heikenwalder","full_name":"Heikenwalder, Mathias","first_name":"Mathias"},{"full_name":"Borsig, Lubor","last_name":"Borsig","first_name":"Lubor"}],"article_processing_charge":"No","external_id":{"isi":["000726603400001"],"pmid":["34868988"]},"article_number":"765151"},{"abstract":[{"lang":"eng","text":"Unpaired ligands are secreted signals that act via a GP130-like receptor, domeless, to activate JAK/STAT signalling in Drosophila. Like many mammalian cytokines, unpaireds can be activated by infection and other stresses and can promote insulin resistance in target tissues. However, the importance of this effect in non-inflammatory physiology is unknown. Here, we identify a requirement for unpaired-JAK signalling as a metabolic regulator in healthy adult Drosophila muscle. Adult muscles show basal JAK-STAT signalling activity in the absence of any immune challenge. Plasmatocytes (Drosophila macrophages) are an important source of this tonic signal. Loss of the dome receptor on adult muscles significantly reduces lifespan and causes local and systemic metabolic pathology. These pathologies result from hyperactivation of AKT and consequent deregulation of metabolism. Thus, we identify a cytokine signal that must be received in muscle to control AKT activity and metabolic homeostasis."}],"oa_version":"Published Version","scopus_import":"1","month":"01","intvolume":" 9","publication_identifier":{"eissn":["2050084X"]},"publication_status":"published","file":[{"file_id":"7470","checksum":"3a072be843f416c7a7d532a51dc0addb","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2020_eLife_Kierdorf.pdf","date_created":"2020-02-10T08:53:16Z","file_size":4959933,"date_updated":"2020-07-14T12:47:59Z","creator":"dernst"}],"language":[{"iso":"eng"}],"volume":9,"_id":"7466","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","date_updated":"2023-08-17T14:36:39Z","ddc":["570"],"file_date_updated":"2020-07-14T12:47:59Z","department":[{"_id":"DaSi"}],"quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"isi":1,"has_accepted_license":"1","year":"2020","day":"20","publication":"eLife","doi":"10.7554/eLife.51595","date_published":"2020-01-20T00:00:00Z","date_created":"2020-02-09T23:00:51Z","article_number":"e51595","project":[{"name":"Drosophila TNFa´s Funktion in Immunzellen","grant_number":"P29638","call_identifier":"FWF","_id":"253B6E48-B435-11E9-9278-68D0E5697425"}],"citation":{"ieee":"K. Kierdorf et al., “Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila,” eLife, vol. 9. eLife Sciences Publications, 2020.","short":"K. Kierdorf, F. Hersperger, J. Sharrock, C.M. Vincent, P. Ustaoglu, J. Dou, A. György, O. Groß, D.E. Siekhaus, M.S. Dionne, ELife 9 (2020).","apa":"Kierdorf, K., Hersperger, F., Sharrock, J., Vincent, C. M., Ustaoglu, P., Dou, J., … Dionne, M. S. (2020). Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.51595","ama":"Kierdorf K, Hersperger F, Sharrock J, et al. Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. eLife. 2020;9. doi:10.7554/eLife.51595","mla":"Kierdorf, Katrin, et al. “Muscle Function and Homeostasis Require Cytokine Inhibition of AKT Activity in Drosophila.” ELife, vol. 9, e51595, eLife Sciences Publications, 2020, doi:10.7554/eLife.51595.","ista":"Kierdorf K, Hersperger F, Sharrock J, Vincent CM, Ustaoglu P, Dou J, György A, Groß O, Siekhaus DE, Dionne MS. 2020. Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. eLife. 9, e51595.","chicago":"Kierdorf, Katrin, Fabian Hersperger, Jessica Sharrock, Crystal M. Vincent, Pinar Ustaoglu, Jiawen Dou, Attila György, Olaf Groß, Daria E Siekhaus, and Marc S. Dionne. “Muscle Function and Homeostasis Require Cytokine Inhibition of AKT Activity in Drosophila.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.51595."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Kierdorf, Katrin","last_name":"Kierdorf","first_name":"Katrin"},{"first_name":"Fabian","last_name":"Hersperger","full_name":"Hersperger, Fabian"},{"first_name":"Jessica","full_name":"Sharrock, Jessica","last_name":"Sharrock"},{"first_name":"Crystal M.","last_name":"Vincent","full_name":"Vincent, Crystal M."},{"last_name":"Ustaoglu","full_name":"Ustaoglu, Pinar","first_name":"Pinar"},{"full_name":"Dou, Jiawen","last_name":"Dou","first_name":"Jiawen"},{"last_name":"György","orcid":"0000-0002-1819-198X","full_name":"György, Attila","first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Olaf","last_name":"Groß","full_name":"Groß, Olaf"},{"full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E"},{"first_name":"Marc S.","last_name":"Dionne","full_name":"Dionne, Marc S."}],"external_id":{"isi":["000512304800001"]},"article_processing_charge":"No","title":"Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila"},{"_id":"8983","type":"dissertation","status":"public","supervisor":[{"orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E","last_name":"Siekhaus","first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-07T13:24:17Z","ddc":["570"],"department":[{"_id":"DaSi"}],"file_date_updated":"2021-12-31T23:30:04Z","abstract":[{"text":"Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"},{"_id":"CampIT"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"12","publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","file":[{"file_id":"8984","checksum":"ec2797ab7a6f253b35df0572b36d1b43","embargo":"2021-12-30","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2020-12-30T15:34:01Z","file_name":"Thesis_Shamsi_Emtenani_pdfA.pdf","date_updated":"2021-12-31T23:30:04Z","file_size":10848175,"creator":"semtenan"},{"content_type":"application/pdf","embargo_to":"open_access","access_level":"closed","relation":"source_file","checksum":"cc30e6608a9815414024cf548dff3b3a","file_id":"8985","date_updated":"2021-12-31T23:30:04Z","file_size":10073648,"creator":"semtenan","date_created":"2020-12-30T15:37:36Z","file_name":"Thesis_Shamsi_Emtenani_source file.pdf"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"part_of_dissertation","id":"8557","status":"public"},{"id":"6187","status":"public","relation":"part_of_dissertation"}]},"citation":{"mla":"Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983.","short":"S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion, Institute of Science and Technology Austria, 2020.","ieee":"S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,” Institute of Science and Technology Austria, 2020.","ama":"Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion. 2020. doi:10.15479/AT:ISTA:8983","apa":"Emtenani, S. (2020). Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8983","chicago":"Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue Invasion.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8983.","ista":"Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"id":"49D32318-F248-11E8-B48F-1D18A9856A87","first_name":"Shamsi","last_name":"Emtenani","full_name":"Emtenani, Shamsi","orcid":"0000-0001-6981-6938"}],"article_processing_charge":"No","title":"Metabolic regulation of Drosophila macrophage tissue invasion","acknowledgement":"Also, I would like to express my appreciation and thanks to the Bioimaging facility, LSF, GSO, library, and IT people at IST Austria.","publisher":"Institute of Science and Technology Austria","oa":1,"has_accepted_license":"1","year":"2020","day":"30","page":"141","date_published":"2020-12-30T00:00:00Z","doi":"10.15479/AT:ISTA:8983","date_created":"2020-12-30T15:41:26Z"},{"year":"2020","publication_status":"submitted","publication":"bioRxiv","language":[{"iso":"eng"}],"day":"18","date_created":"2020-09-23T09:36:47Z","ec_funded":1,"date_published":"2020-09-18T00:00:00Z","doi":"10.1101/2020.09.18.301481","related_material":{"record":[{"relation":"later_version","id":"10614","status":"public"},{"relation":"dissertation_contains","status":"public","id":"8983"}]},"acknowledged_ssus":[{"_id":"LifeSc"}],"abstract":[{"text":"The infiltration of immune cells into tissues underlies the establishment of tissue resident macrophages, and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio which are themselves required for invasion. Cortical F-actin levels are critical as expressing a dominant active form of Diaphanous, a actin polymerizing Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo imaging shows that Dfos is required to enhance the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the mechanical properties of the macrophage nucleus from affecting tissue entry. We thus identify tuning the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.","lang":"eng"}],"acknowledgement":"We thank the following for their contributions: The Drosophila Genomics Resource Center supported by NIH grant 2P40OD010949-10A1 for plasmids, K. Brueckner. B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center supported by NIH grant P40OD018537 and the Vienna Drosophila Resource Center for fly stocks, FlyBase (Thurmond et al., 2019) for essential genomic information, and the BDGP in situ database for data (Tomancak et al., 2002, 2007). For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH, and is maintained at the University of Iowa, as well as J. Zeitlinger for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria for technical support and assistance with microscopy and FACS analysis. We thank C.P. Heisenberg, P. Martin, M. Sixt and Siekhaus group members for discussions and T.Hurd, A. Ratheesh and P. Rangan for comments on the manuscript. A.G. was supported by the Austrian Science Fund (FWF) grant DASI_FWF01_P29638S, D.E.S. by Marie Curie CIG 334077/IRTIM. M.S. is supported by the FWF, PhD program W1212 915 and the European Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883). S.W. is supported by an OEAW, DOC fellowship.","oa_version":"Preprint","main_file_link":[{"url":"https://doi.org/10.1101/2020.09.18.301481","open_access":"1"}],"oa":1,"month":"09","date_updated":"2024-03-27T23:30:24Z","citation":{"ista":"Belyaeva V, Wachner S, Gridchyn I, Linder M, Emtenani S, György A, Sibilia M, Siekhaus DE. Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv, 10.1101/2020.09.18.301481.","chicago":"Belyaeva, Vera, Stephanie Wachner, Igor Gridchyn, Markus Linder, Shamsi Emtenani, Attila György, Maria Sibilia, and Daria E Siekhaus. “Cortical Actin Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv, n.d. https://doi.org/10.1101/2020.09.18.301481.","ama":"Belyaeva V, Wachner S, Gridchyn I, et al. Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv. doi:10.1101/2020.09.18.301481","apa":"Belyaeva, V., Wachner, S., Gridchyn, I., Linder, M., Emtenani, S., György, A., … Siekhaus, D. E. (n.d.). Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv. https://doi.org/10.1101/2020.09.18.301481","ieee":"V. Belyaeva et al., “Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance,” bioRxiv. .","short":"V. Belyaeva, S. Wachner, I. Gridchyn, M. Linder, S. Emtenani, A. György, M. Sibilia, D.E. Siekhaus, BioRxiv (n.d.).","mla":"Belyaeva, Vera, et al. “Cortical Actin Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv, doi:10.1101/2020.09.18.301481."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","author":[{"full_name":"Belyaeva, Vera","last_name":"Belyaeva","first_name":"Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Wachner","full_name":"Wachner, Stephanie","first_name":"Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-1807-1929","full_name":"Gridchyn, Igor","last_name":"Gridchyn","id":"4B60654C-F248-11E8-B48F-1D18A9856A87","first_name":"Igor"},{"full_name":"Linder, Markus","last_name":"Linder","first_name":"Markus"},{"last_name":"Emtenani","orcid":"0000-0001-6981-6938","full_name":"Emtenani, Shamsi","first_name":"Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","orcid":"0000-0002-1819-198X","full_name":"György, Attila"},{"full_name":"Sibilia, Maria","last_name":"Sibilia","first_name":"Maria"},{"first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus"}],"title":"Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance","department":[{"_id":"DaSi"},{"_id":"JoCs"}],"_id":"8557","type":"preprint","project":[{"name":"Drosophila TNFa´s Funktion in Immunzellen","grant_number":"P29638","_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Investigating the role of transporters in invasive migration through junctions","grant_number":"334077"},{"name":"Tissue barrier penetration is crucial for immunity and metastasis","grant_number":"24800","_id":"26199CA4-B435-11E9-9278-68D0E5697425"}],"status":"public"},{"_id":"6190","article_type":"original","type":"journal_article","status":"public","date_updated":"2023-08-25T08:57:01Z","department":[{"_id":"DaSi"}],"abstract":[{"lang":"eng","text":"Increased levels of the chemokine CCL2 in cancer patients are associated with poor prognosis. Experimental evidence suggests that CCL2 correlates with inflammatory monocyte recruitment and induction of vascular activation, but the functionality remains open. Here, we show that endothelial Ccr2 facilitates pulmonary metastasis using an endothelial-specific Ccr2-deficient mouse model (Ccr2ecKO). Similar levels of circulating monocytes and equal leukocyte recruitment to metastatic lesions of Ccr2ecKO and Ccr2fl/fl littermates were observed. The absence of endothelial Ccr2 strongly reduced pulmonary metastasis, while the primary tumor growth was unaffected. Despite a comparable cytokine milieu in Ccr2ecKO and Ccr2fl/fl littermates the absence of vascular permeability induction was observed only in Ccr2ecKO mice. CCL2 stimulation of pulmonary endothelial cells resulted in increased phosphorylation of MLC2, endothelial cell retraction, and vascular leakiness that was blocked by an addition of a CCR2 inhibitor. These data demonstrate that endothelial CCR2 expression is required for tumor cell extravasation and pulmonary metastasis.\r\n\r\nImplications: The findings provide mechanistic insight into how CCL2–CCR2 signaling in endothelial cells promotes their activation through myosin light chain phosphorylation, resulting in endothelial retraction and enhanced tumor cell migration and metastasis."}],"oa_version":"Published Version","pmid":1,"main_file_link":[{"url":"https://doi.org/10.1158/1541-7786.MCR-18-0530","open_access":"1"}],"scopus_import":"1","intvolume":" 17","month":"03","publication_status":"published","publication_identifier":{"issn":["15417786"],"eissn":["15573125"]},"language":[{"iso":"eng"}],"volume":17,"issue":"3","citation":{"ista":"Roblek M, Protsyuk D, Becker PF, Stefanescu C, Gorzelanny C, Glaus Garzon JF, Knopfova L, Heikenwalder M, Luckow B, Schneider SW, Borsig L. 2019. CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis. Molecular Cancer Research. 17(3), 783–793.","chicago":"Roblek, Marko, Darya Protsyuk, Paul F. Becker, Cristina Stefanescu, Christian Gorzelanny, Jesus F. Glaus Garzon, Lucia Knopfova, et al. “CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis.” Molecular Cancer Research. AACR, 2019. https://doi.org/10.1158/1541-7786.MCR-18-0530.","ama":"Roblek M, Protsyuk D, Becker PF, et al. CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis. Molecular Cancer Research. 2019;17(3):783-793. doi:10.1158/1541-7786.MCR-18-0530","apa":"Roblek, M., Protsyuk, D., Becker, P. F., Stefanescu, C., Gorzelanny, C., Glaus Garzon, J. F., … Borsig, L. (2019). CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis. Molecular Cancer Research. AACR. https://doi.org/10.1158/1541-7786.MCR-18-0530","ieee":"M. Roblek et al., “CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis,” Molecular Cancer Research, vol. 17, no. 3. AACR, pp. 783–793, 2019.","short":"M. Roblek, D. Protsyuk, P.F. Becker, C. Stefanescu, C. Gorzelanny, J.F. Glaus Garzon, L. Knopfova, M. Heikenwalder, B. Luckow, S.W. Schneider, L. Borsig, Molecular Cancer Research 17 (2019) 783–793.","mla":"Roblek, Marko, et al. “CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis.” Molecular Cancer Research, vol. 17, no. 3, AACR, 2019, pp. 783–93, doi:10.1158/1541-7786.MCR-18-0530."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"pmid":["30552233"],"isi":["000460099800012"]},"article_processing_charge":"No","author":[{"id":"3047D808-F248-11E8-B48F-1D18A9856A87","first_name":"Marko","last_name":"Roblek","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko"},{"last_name":"Protsyuk","full_name":"Protsyuk, Darya","first_name":"Darya"},{"first_name":"Paul F.","full_name":"Becker, Paul F.","last_name":"Becker"},{"full_name":"Stefanescu, Cristina","last_name":"Stefanescu","first_name":"Cristina"},{"first_name":"Christian","last_name":"Gorzelanny","full_name":"Gorzelanny, Christian"},{"first_name":"Jesus F.","full_name":"Glaus Garzon, Jesus F.","last_name":"Glaus Garzon"},{"last_name":"Knopfova","full_name":"Knopfova, Lucia","first_name":"Lucia"},{"last_name":"Heikenwalder","full_name":"Heikenwalder, Mathias","first_name":"Mathias"},{"first_name":"Bruno","full_name":"Luckow, Bruno","last_name":"Luckow"},{"first_name":"Stefan W.","full_name":"Schneider, Stefan W.","last_name":"Schneider"},{"full_name":"Borsig, Lubor","last_name":"Borsig","first_name":"Lubor"}],"title":"CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis","oa":1,"quality_controlled":"1","publisher":"AACR","year":"2019","isi":1,"publication":"Molecular Cancer Research","day":"01","page":"783-793","date_created":"2019-03-31T21:59:12Z","date_published":"2019-03-01T00:00:00Z","doi":"10.1158/1541-7786.MCR-18-0530"},{"volume":2,"issue":"1","publication_status":"published","publication_identifier":{"issn":["2399-3642"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"c63c69a264fc8a0e52f2b0d482f3bdae","file_id":"7098","date_updated":"2020-07-14T12:47:49Z","file_size":2626069,"creator":"dernst","date_created":"2019-11-25T07:58:05Z","file_name":"2019_CommunicBiology_Nagano.pdf"}],"scopus_import":"1","intvolume":" 2","month":"11","abstract":[{"lang":"eng","text":"Early endosomes, also called sorting endosomes, are known to mature into late endosomesvia the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence isthought to be maintained by the continual fusion of transport vesicles from the plasmamembrane and thetrans-Golgi network (TGN). Here we show instead that endocytosis isdispensable and post-Golgi vesicle transport is crucial for the formation of endosomes andthe subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all threeproteins required for endosomal nucleotide exchange on Vps21p arefirst recruited to theTGN before transport to the endosome, namely the GEF Vps9p and the epsin-relatedadaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, withVps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These resultsprovide a different view of endosome formation and identify the TGN as a critical location forregulating progress through the endolysosomal trafficking pathway."}],"oa_version":"Published Version","file_date_updated":"2020-07-14T12:47:49Z","department":[{"_id":"DaSi"}],"date_updated":"2023-08-30T07:27:55Z","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","status":"public","_id":"7097","date_created":"2019-11-25T07:55:01Z","date_published":"2019-11-15T00:00:00Z","doi":"10.1038/s42003-019-0670-5","year":"2019","has_accepted_license":"1","isi":1,"publication":"Communications Biology","day":"15","oa":1,"publisher":"Springer Nature","quality_controlled":"1","external_id":{"isi":["000496767800005"]},"article_processing_charge":"No","author":[{"first_name":"Makoto","full_name":"Nagano, Makoto","last_name":"Nagano"},{"first_name":"Junko Y.","last_name":"Toshima","full_name":"Toshima, Junko Y."},{"last_name":"Siekhaus","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E"},{"last_name":"Toshima","full_name":"Toshima, Jiro","first_name":"Jiro"}],"title":"Rab5-mediated endosome formation is regulated at the trans-Golgi network","citation":{"short":"M. Nagano, J.Y. Toshima, D.E. Siekhaus, J. Toshima, Communications Biology 2 (2019).","ieee":"M. Nagano, J. Y. Toshima, D. E. Siekhaus, and J. Toshima, “Rab5-mediated endosome formation is regulated at the trans-Golgi network,” Communications Biology, vol. 2, no. 1. Springer Nature, 2019.","ama":"Nagano M, Toshima JY, Siekhaus DE, Toshima J. Rab5-mediated endosome formation is regulated at the trans-Golgi network. Communications Biology. 2019;2(1). doi:10.1038/s42003-019-0670-5","apa":"Nagano, M., Toshima, J. Y., Siekhaus, D. E., & Toshima, J. (2019). Rab5-mediated endosome formation is regulated at the trans-Golgi network. Communications Biology. Springer Nature. https://doi.org/10.1038/s42003-019-0670-5","mla":"Nagano, Makoto, et al. “Rab5-Mediated Endosome Formation Is Regulated at the Trans-Golgi Network.” Communications Biology, vol. 2, no. 1, 419, Springer Nature, 2019, doi:10.1038/s42003-019-0670-5.","ista":"Nagano M, Toshima JY, Siekhaus DE, Toshima J. 2019. Rab5-mediated endosome formation is regulated at the trans-Golgi network. Communications Biology. 2(1), 419.","chicago":"Nagano, Makoto, Junko Y. Toshima, Daria E Siekhaus, and Jiro Toshima. “Rab5-Mediated Endosome Formation Is Regulated at the Trans-Golgi Network.” Communications Biology. Springer Nature, 2019. https://doi.org/10.1038/s42003-019-0670-5."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_number":"419"},{"publisher":"Springer Nature","quality_controlled":"1","oa":1,"doi":"10.1038/s41467-019-13543-1","date_published":"2019-12-01T00:00:00Z","date_created":"2019-12-15T23:00:43Z","day":"01","publication":"Nature Communications","isi":1,"has_accepted_license":"1","year":"2019","project":[{"grant_number":"M02379","name":"Modeling epithelial tissue mechanics during cell invasion","call_identifier":"FWF","_id":"264CBBAC-B435-11E9-9278-68D0E5697425"}],"article_number":"5516","title":"Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter","author":[{"last_name":"Retzer","full_name":"Retzer, Katarzyna","first_name":"Katarzyna"},{"first_name":"Maria","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","last_name":"Akhmanova","full_name":"Akhmanova, Maria","orcid":"0000-0003-1522-3162"},{"last_name":"Konstantinova","full_name":"Konstantinova, Nataliia","first_name":"Nataliia"},{"full_name":"Malínská, Kateřina","last_name":"Malínská","first_name":"Kateřina"},{"first_name":"Johannes","last_name":"Leitner","full_name":"Leitner, Johannes"},{"full_name":"Petrášek, Jan","last_name":"Petrášek","first_name":"Jan"},{"last_name":"Luschnig","full_name":"Luschnig, Christian","first_name":"Christian"}],"article_processing_charge":"No","external_id":{"isi":["000500508100001"],"pmid":["31797871"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"short":"K. Retzer, M. Akhmanova, N. Konstantinova, K. Malínská, J. Leitner, J. Petrášek, C. Luschnig, Nature Communications 10 (2019).","ieee":"K. Retzer et al., “Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter,” Nature Communications, vol. 10. Springer Nature, 2019.","apa":"Retzer, K., Akhmanova, M., Konstantinova, N., Malínská, K., Leitner, J., Petrášek, J., & Luschnig, C. (2019). Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-13543-1","ama":"Retzer K, Akhmanova M, Konstantinova N, et al. Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter. Nature Communications. 2019;10. doi:10.1038/s41467-019-13543-1","mla":"Retzer, Katarzyna, et al. “Brassinosteroid Signaling Delimits Root Gravitropism via Sorting of the Arabidopsis PIN2 Auxin Transporter.” Nature Communications, vol. 10, 5516, Springer Nature, 2019, doi:10.1038/s41467-019-13543-1.","ista":"Retzer K, Akhmanova M, Konstantinova N, Malínská K, Leitner J, Petrášek J, Luschnig C. 2019. Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter. Nature Communications. 10, 5516.","chicago":"Retzer, Katarzyna, Maria Akhmanova, Nataliia Konstantinova, Kateřina Malínská, Johannes Leitner, Jan Petrášek, and Christian Luschnig. “Brassinosteroid Signaling Delimits Root Gravitropism via Sorting of the Arabidopsis PIN2 Auxin Transporter.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-13543-1."},"month":"12","intvolume":" 10","scopus_import":"1","pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Arabidopsis PIN2 protein directs transport of the phytohormone auxin from the root tip into the root elongation zone. Variation in hormone transport, which depends on a delicate interplay between PIN2 sorting to and from polar plasma membrane domains, determines root growth. By employing a constitutively degraded version of PIN2, we identify brassinolides as antagonists of PIN2 endocytosis. This response does not require de novo protein synthesis, but involves early events in canonical brassinolide signaling. Brassinolide-controlled adjustments in PIN2 sorting and intracellular distribution governs formation of a lateral PIN2 gradient in gravistimulated roots, coinciding with adjustments in auxin signaling and directional root growth. Strikingly, simulations indicate that PIN2 gradient formation is no prerequisite for root bending but rather dampens asymmetric auxin flow and signaling. Crosstalk between brassinolide signaling and endocytic PIN2 sorting, thus, appears essential for determining the rate of gravity-induced root curvature via attenuation of differential cell elongation."}],"volume":10,"file":[{"checksum":"77e8720a8e0f3091b98159f85be40893","file_id":"7184","access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2019-12-16T07:37:50Z","file_name":"2019_NatureComm_Retzer.pdf","creator":"dernst","date_updated":"2020-07-14T12:47:52Z","file_size":5156533}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["20411723"]},"publication_status":"published","status":"public","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"7180","file_date_updated":"2020-07-14T12:47:52Z","department":[{"_id":"DaSi"}],"ddc":["570"],"date_updated":"2023-09-06T14:08:21Z"},{"acknowledgement":"This work was supported by INSERM, CNRS, UDS, Ligue Régionale contre le Cancer, Hôpital de Strasbourg, Association pour la Recherche sur le Cancer (ARC) and Agence Nationale de la Recherche (ANR) grants. P.B.C. was funded by the ANR and by the ARSEP (Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques), and G.T. by governmental and ARC fellowships. This work was also supported by grants from the Ataxia UK (2491) and the NC3R (NC/L000199/1) awarded to M.F. The Institut de Génétique et de Biologie Moléculaire et Cellulaire was also supported by a French state fund through the ANR labex. D.E.S. was funded by Marie Curie Grant CIG 334077/IRTIM. We thank B. Altenhein, K. Brückner, M. Crozatier, L. Waltzer, M. Logan, E. Kurant, R. Reuter, E. Kurucz, J.L Dimarcq, J. Hoffmann, C. Goodman, the DHSB, and the BDSC for reagents and flies. We also thank all of the laboratory members for comments on the manuscript; C. Diebold, C. Delaporte, M. Pezze, the fly, and imaging and antibody facilities for technical assistance; and D. Dembele for help with statistics. In addition, we thank Alison Brewer for help with Luciferase assays.","oa":1,"quality_controlled":"1","publisher":"Society for Neuroscience","year":"2019","has_accepted_license":"1","isi":1,"publication":"Journal of Neuroscience","day":"09","page":"238-255","date_created":"2018-12-11T11:44:07Z","doi":"10.1523/JNEUROSCI.1059-18.2018","date_published":"2019-01-09T00:00:00Z","project":[{"_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Investigating the role of transporters in invasive migration through junctions","grant_number":"334077"}],"citation":{"apa":"Trébuchet, G., Cattenoz, P. B., Zsámboki, J., Mazaud, D., Siekhaus, D. E., Fanto, M., & Giangrande, A. (2019). The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1059-18.2018","ama":"Trébuchet G, Cattenoz PB, Zsámboki J, et al. The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. 2019;39(2):238-255. doi:10.1523/JNEUROSCI.1059-18.2018","ieee":"G. Trébuchet et al., “The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate,” Journal of Neuroscience, vol. 39, no. 2. Society for Neuroscience, pp. 238–255, 2019.","short":"G. Trébuchet, P.B. Cattenoz, J. Zsámboki, D. Mazaud, D.E. Siekhaus, M. Fanto, A. Giangrande, Journal of Neuroscience 39 (2019) 238–255.","mla":"Trébuchet, Guillaume, et al. “The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis in Drosophila and Preserves the Glial Fate.” Journal of Neuroscience, vol. 39, no. 2, Society for Neuroscience, 2019, pp. 238–55, doi:10.1523/JNEUROSCI.1059-18.2018.","ista":"Trébuchet G, Cattenoz PB, Zsámboki J, Mazaud D, Siekhaus DE, Fanto M, Giangrande A. 2019. The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. 39(2), 238–255.","chicago":"Trébuchet, Guillaume, Pierre B Cattenoz, János Zsámboki, David Mazaud, Daria E Siekhaus, Manolis Fanto, and Angela Giangrande. “The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis in Drosophila and Preserves the Glial Fate.” Journal of Neuroscience. Society for Neuroscience, 2019. https://doi.org/10.1523/JNEUROSCI.1059-18.2018."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","external_id":{"isi":["000455189900006"],"pmid":["30504274"]},"publist_id":"8048","author":[{"last_name":"Trébuchet","full_name":"Trébuchet, Guillaume","first_name":"Guillaume"},{"first_name":"Pierre B","last_name":"Cattenoz","full_name":"Cattenoz, Pierre B"},{"first_name":"János","full_name":"Zsámboki, János","last_name":"Zsámboki"},{"first_name":"David","last_name":"Mazaud","full_name":"Mazaud, David"},{"first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E","last_name":"Siekhaus"},{"full_name":"Fanto, Manolis","last_name":"Fanto","first_name":"Manolis"},{"first_name":"Angela","full_name":"Giangrande, Angela","last_name":"Giangrande"}],"title":"The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate","abstract":[{"text":"Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside the nervous system (hemocytes) require the same transcription factor Glide/Gcm for their development. This raises the issue of how do glia specifically differentiate in the nervous system and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and pan-glial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us understand the bases of cell specification. Both sexes were analyzed.SIGNIFICANCE STATEMENTDistinct cell types often require the same pioneer transcription factor, raising the issue of how does one factor trigger different fates. In Drosophila, glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the Glide/Gcm transcription factor, glia originate from the ectoderm, hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification.","lang":"eng"}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","intvolume":" 39","month":"01","publication_status":"published","language":[{"iso":"eng"}],"file":[{"file_name":"2019_JournNeuroscience_Trebuchet.pdf","date_created":"2020-10-02T09:33:28Z","file_size":9455414,"date_updated":"2020-10-02T09:33:28Z","creator":"dernst","success":1,"file_id":"8596","checksum":"8f6925eb4cd1e8747d8ea25929c68de6","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"ec_funded":1,"issue":"2","volume":39,"_id":"8","article_type":"original","type":"journal_article","status":"public","date_updated":"2023-09-19T10:10:55Z","ddc":["570"],"department":[{"_id":"DaSi"}],"file_date_updated":"2020-10-02T09:33:28Z"},{"article_number":"e41801","project":[{"_id":"253CDE40-B435-11E9-9278-68D0E5697425","name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells","grant_number":"24283"},{"call_identifier":"FWF","_id":"253B6E48-B435-11E9-9278-68D0E5697425","name":"The role of Drosophila TNF alpha in immune cell invasion","grant_number":"P29638"},{"name":"Investigating the role of transporters in invasive migration through junctions","grant_number":"334077","call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425"},{"name":"Breaking barriers: Investigating the junctional and mechanobiological changes underlying the ability of Drosophila immune cells to invade an epithelium","grant_number":"329540","call_identifier":"FP7","_id":"25388084-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE. 2019. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801.","chicago":"Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.41801.","short":"K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A. Ratheesh, P. Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev, H. Clausen, D.E. Siekhaus, ELife 8 (2019).","ieee":"K. Valosková et al., “A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” eLife, vol. 8. eLife Sciences Publications, 2019.","ama":"Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 2019;8. doi:10.7554/elife.41801","apa":"Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M., … Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.41801","mla":"Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife, vol. 8, e41801, eLife Sciences Publications, 2019, doi:10.7554/elife.41801."},"title":"A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion","external_id":{"isi":["000462530200001"]},"article_processing_charge":"No","author":[{"full_name":"Valosková, Katarina","last_name":"Valosková","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","first_name":"Katarina"},{"id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Biebl","full_name":"Biebl, Julia"},{"first_name":"Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko","last_name":"Roblek"},{"first_name":"Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87","last_name":"Emtenani","full_name":"Emtenani, Shamsi","orcid":"0000-0001-6981-6938"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","last_name":"György","first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Misova","full_name":"Misova, Michaela","orcid":"0000-0003-2427-6856","id":"495A3C32-F248-11E8-B48F-1D18A9856A87","first_name":"Michaela"},{"orcid":"0000-0001-7190-0776","full_name":"Ratheesh, Aparna","last_name":"Ratheesh","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","first_name":"Aparna"},{"first_name":"Patricia","id":"2CE4065A-F248-11E8-B48F-1D18A9856A87","full_name":"Rodrigues, Patricia","last_name":"Rodrigues"},{"first_name":"Katerina","full_name":"Shkarina, Katerina","last_name":"Shkarina"},{"last_name":"Larsen","full_name":"Larsen, Ida Signe Bohse","first_name":"Ida Signe Bohse"},{"first_name":"Sergey Y","full_name":"Vakhrushev, Sergey Y","last_name":"Vakhrushev"},{"full_name":"Clausen, Henrik","last_name":"Clausen","first_name":"Henrik"},{"last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"publisher":"eLife Sciences Publications","quality_controlled":"1","publication":"eLife","day":"26","year":"2019","has_accepted_license":"1","isi":1,"date_created":"2019-03-28T13:37:45Z","doi":"10.7554/elife.41801","date_published":"2019-03-26T00:00:00Z","_id":"6187","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","ddc":["570"],"date_updated":"2024-03-27T23:30:29Z","file_date_updated":"2020-07-14T12:47:23Z","department":[{"_id":"DaSi"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"LifeSc"}],"abstract":[{"text":"Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis.","lang":"eng"}],"intvolume":" 8","month":"03","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"date_updated":"2020-07-14T12:47:23Z","file_size":4496017,"creator":"dernst","date_created":"2019-03-28T14:00:41Z","file_name":"2019_eLife_Valoskova.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"cc0d1a512559d52e7e7cb0e9b9854b40","file_id":"6188"}],"publication_status":"published","publication_identifier":{"issn":["2050-084X"]},"ec_funded":1,"related_material":{"record":[{"relation":"dissertation_contains","id":"6530"},{"id":"8983","status":"public","relation":"dissertation_contains"},{"status":"public","id":"6546","relation":"dissertation_contains"}],"link":[{"url":"https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/","relation":"press_release","description":"News on IST Homepage"}]},"volume":8},{"related_material":{"record":[{"id":"6187","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"544","relation":"part_of_dissertation"}]},"file":[{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","access_level":"closed","relation":"source_file","file_id":"6549","checksum":"68949c2d96210b45b981a23e9c9cd93c","date_updated":"2020-07-14T12:47:33Z","file_size":14110626,"creator":"khribikova","date_created":"2019-06-07T13:00:04Z","file_name":"Katarina Valoskova_PhD thesis_final version.docx"},{"embargo":"2020-06-07","checksum":"555329cd76e196c96f5278c480ee2e6e","file_id":"6550","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"Katarina Valoskova_PhD thesis_final version.pdf","date_created":"2019-06-07T13:00:08Z","creator":"khribikova","file_size":10054156,"date_updated":"2021-02-11T11:17:14Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","month":"06","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation. \r\n\r\nAberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify \r\na key conserved regulator that orchestrates O-glycosylation on a protein subset to activate \r\na program governing migration steps important for both development and cancer metastasis. \r\n"}],"acknowledged_ssus":[{"_id":"Bio"}],"file_date_updated":"2021-02-11T11:17:14Z","department":[{"_id":"DaSi"}],"ddc":["570"],"supervisor":[{"full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus","first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-19T10:15:54Z","status":"public","type":"dissertation","_id":"6546","date_published":"2019-06-07T00:00:00Z","doi":"10.15479/AT:ISTA:6546","date_created":"2019-06-07T12:49:19Z","page":"141","day":"07","has_accepted_license":"1","year":"2019","publisher":"Institute of Science and Technology Austria","oa":1,"title":"The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration","author":[{"first_name":"Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","last_name":"Valosková","full_name":"Valosková, Katarina"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Valosková K. 2019. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria.","chicago":"Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546.","ama":"Valosková K. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546","apa":"Valosková, K. (2019). The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546","ieee":"K. Valosková, “The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration,” Institute of Science and Technology Austria, 2019.","short":"K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration, Institute of Science and Technology Austria, 2019.","mla":"Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546."},"project":[{"_id":"253CDE40-B435-11E9-9278-68D0E5697425","name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells","grant_number":"24283"}]}]