--- _id: '14316' abstract: - lang: eng 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. article_number: jcs261448 article_processing_charge: No article_type: original author: - first_name: Makoto full_name: Nagano, Makoto last_name: Nagano - first_name: Kaito full_name: Aoshima, Kaito last_name: Aoshima - first_name: Hiroki full_name: Shimamura, Hiroki last_name: Shimamura - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 - first_name: Junko Y. full_name: Toshima, Junko Y. last_name: Toshima - first_name: Jiro full_name: Toshima, Jiro last_name: Toshima citation: 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 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 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. 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. 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. 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. short: M. Nagano, K. Aoshima, H. Shimamura, D.E. Siekhaus, J.Y. Toshima, J. Toshima, Journal of Cell Science 136 (2023). date_created: 2023-09-10T22:01:12Z date_published: 2023-09-01T00:00:00Z date_updated: 2023-09-20T09:14:15Z day: '01' department: - _id: DaSi doi: 10.1242/jcs.261448 external_id: pmid: - '37539494' intvolume: ' 136' issue: '17' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2023.03.27.534325 month: '09' oa: 1 oa_version: Preprint pmid: 1 publication: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - 0021-9533 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: Distinct role of TGN-resident clathrin adaptors for Vps21p activation in the TGN-endosome trafficking pathway type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 136 year: '2023' ... --- _id: '13316' 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. 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.' article_number: e84850 article_processing_charge: Yes article_type: original author: - first_name: Junko Y. full_name: Toshima, Junko Y. last_name: Toshima - first_name: Ayana full_name: Tsukahara, Ayana last_name: Tsukahara - first_name: Makoto full_name: Nagano, Makoto last_name: Nagano - first_name: Takuro full_name: Tojima, Takuro last_name: Tojima - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 - first_name: Akihiko full_name: Nakano, Akihiko last_name: Nakano - first_name: Jiro full_name: Toshima, Jiro last_name: Toshima citation: 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. 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. 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. 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. short: J.Y. Toshima, A. Tsukahara, M. Nagano, T. Tojima, D.E. Siekhaus, A. Nakano, J. Toshima, ELife 12 (2023). date_created: 2023-07-30T22:01:02Z date_published: 2023-07-21T00:00:00Z date_updated: 2023-12-13T11:37:36Z day: '21' ddc: - '570' department: - _id: DaSi doi: 10.7554/eLife.84850 external_id: isi: - '001035372800001' pmid: - '37477116' file: - access_level: open_access checksum: 2af111a00cf5e3a956f7f0fd13199b15 content_type: application/pdf creator: dernst date_created: 2023-07-31T07:43:00Z date_updated: 2023-07-31T07:43:00Z file_id: '13324' file_name: 2023_eLife_Toshima.pdf file_size: 11980913 relation: main_file success: 1 file_date_updated: 2023-07-31T07:43:00Z has_accepted_license: '1' intvolume: ' 12' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 12 year: '2023' ... --- _id: '10712' abstract: - lang: eng 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. acknowledged_ssus: - _id: Bio 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). article_number: '777634' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: Julia full_name: Bicher, Julia id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87 last_name: Bicher - first_name: Merel full_name: van Gogh, Merel last_name: van Gogh - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Rita full_name: Seeböck, Rita last_name: Seeböck - first_name: Bozena full_name: Szulc, Bozena last_name: Szulc - first_name: Markus full_name: Damme, Markus last_name: Damme - first_name: Mariusz full_name: Olczak, Mariusz last_name: Olczak - first_name: Lubor full_name: Borsig, Lubor last_name: Borsig - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: 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 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 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. 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. 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. 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. 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). date_created: 2022-02-01T10:33:50Z date_published: 2022-02-08T00:00:00Z date_updated: 2023-08-02T14:05:44Z day: '08' ddc: - '570' department: - _id: DaSi doi: 10.3389/fonc.2022.777634 external_id: isi: - '000760618800001' file: - access_level: open_access checksum: 63dfecf30c5bbf9408b3512bd603f78c content_type: application/pdf creator: cchlebak date_created: 2022-02-08T13:26:40Z date_updated: 2022-02-08T13:26:40Z file_id: '10751' file_name: 2022_FrontiersOncol_Roblek.pdf file_size: 6303227 relation: main_file success: 1 file_date_updated: 2022-02-08T13:26:40Z has_accepted_license: '1' intvolume: ' 12' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version project: - _id: 2637E9C0-B435-11E9-9278-68D0E5697425 grant_number: 'LSC16-021 ' name: Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis publication: Frontiers in Oncology publication_identifier: issn: - 2234-943X publication_status: published publisher: Frontiers quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: confirmation url: https://ist.ac.at/en/news/suppressing-the-spread-of-tumors/ scopus_import: '1' status: public title: The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2022' ... --- _id: '10714' abstract: - lang: eng 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. 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. article_processing_charge: No article_type: original author: - first_name: Elliot T. full_name: Martin, Elliot T. last_name: Martin - first_name: Patrick full_name: Blatt, Patrick last_name: Blatt - first_name: Elaine full_name: Ngyuen, Elaine last_name: Ngyuen - 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. full_name: Yoon, Hyun Ah M. last_name: Yoon - first_name: Tyler full_name: Pocchiari, Tyler last_name: Pocchiari - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 - first_name: Andrea full_name: Berman, Andrea last_name: Berman - first_name: Gabriele full_name: Fuchs, Gabriele last_name: Fuchs - first_name: Prashanth full_name: Rangan, Prashanth last_name: Rangan 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 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. 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. 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. 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. 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. date_created: 2022-02-01T13:15:05Z date_published: 2022-04-11T00:00:00Z date_updated: 2023-08-02T14:07:13Z day: '11' department: - _id: DaSi doi: 10.1016/j.devcel.2022.03.005 ec_funded: 1 external_id: isi: - '000789021800005' intvolume: ' 57' isi: 1 issue: '7' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ main_file_link: - open_access: '1' url: https://doi.org/10.1101/2021.04.04.438367 month: '04' oa: 1 oa_version: Preprint page: 883-900.e10 project: - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: Drosophila TNFa´s Funktion in Immunzellen publication: Developmental Cell publication_identifier: eissn: - 1878-1551 issn: - 1534-5807 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 57 year: '2022' ... --- _id: '10713' abstract: - lang: eng 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. acknowledged_ssus: - _id: Bio 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.' article_processing_charge: No article_type: original author: - first_name: Maria full_name: Akhmanova, Maria id: 3425EC26-F248-11E8-B48F-1D18A9856A87 last_name: Akhmanova orcid: 0000-0003-1522-3162 - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Daniel full_name: Krueger, Daniel last_name: Krueger - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Mariana full_name: Pereira Guarda, Mariana id: 6de81d9d-e2f2-11eb-945a-af8bc2a60b26 last_name: Pereira Guarda - first_name: Mikhail full_name: Vlasov, Mikhail last_name: Vlasov - first_name: Fedor full_name: Vlasov, Fedor last_name: Vlasov - first_name: Andrei full_name: Akopian, Andrei last_name: Akopian - first_name: Aparna full_name: Ratheesh, Aparna id: 2F064CFE-F248-11E8-B48F-1D18A9856A87 last_name: Ratheesh - first_name: Stefano full_name: De Renzis, Stefano last_name: De Renzis - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: 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 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. 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. 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. date_created: 2022-02-01T11:23:18Z date_published: 2022-04-22T00:00:00Z date_updated: 2023-08-02T14:06:15Z day: '22' department: - _id: DaSi doi: 10.1126/science.abj0425 external_id: isi: - '000788553700039' pmid: - '35446632' intvolume: ' 376' isi: 1 issue: '6591' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2021.04.19.438995 month: '04' oa: 1 oa_version: Preprint page: 394-396 pmid: 1 project: - _id: 264CBBAC-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02379 name: Modeling epithelial tissue mechanics during cell invasion publication: Science publication_identifier: issn: - 0036-8075 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' status: public title: Cell division in tissues enables macrophage infiltration tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 376 year: '2022' ... --- _id: '10918' 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 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). " article_number: e109049 article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Elliot T full_name: Martin, Elliot T last_name: Martin - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Julia full_name: Bicher, Julia id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87 last_name: Bicher - first_name: Jakob-Wendelin full_name: Genger, Jakob-Wendelin last_name: Genger - first_name: Thomas full_name: Köcher, Thomas last_name: Köcher - first_name: Maria full_name: Akhmanova, Maria id: 3425EC26-F248-11E8-B48F-1D18A9856A87 last_name: Akhmanova orcid: 0000-0003-1522-3162 - first_name: Mariana full_name: Pereira Guarda, Mariana id: 6de81d9d-e2f2-11eb-945a-af8bc2a60b26 last_name: Pereira Guarda - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: Andreas full_name: Bergthaler, Andreas last_name: Bergthaler - first_name: Thomas R full_name: Hurd, Thomas R last_name: Hurd - first_name: Prashanth full_name: Rangan, Prashanth last_name: Rangan - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: 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 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. 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. 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. 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. 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). date_created: 2022-03-24T13:23:09Z date_published: 2022-03-23T00:00:00Z date_updated: 2023-08-03T06:13:14Z day: '23' ddc: - '570' department: - _id: DaSi - _id: LoSw doi: 10.15252/embj.2021109049 ec_funded: 1 external_id: isi: - '000771957000001' file: - access_level: open_access checksum: dba48580fe0fefaa4c63078d1d2a35df content_type: application/pdf creator: siekhaus date_created: 2022-03-24T13:22:41Z date_updated: 2022-03-24T13:22:41Z file_id: '10919' file_name: Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosopila.pdf file_size: 4344585 relation: main_file file_date_updated: 2022-03-24T13:22:41Z has_accepted_license: '1' intvolume: ' 41' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version project: - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions - _id: 264CBBAC-B435-11E9-9278-68D0E5697425 call_identifier: FWF 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 publication: The Embo Journal publication_identifier: eissn: - 1460-2075 publication_status: published publisher: Embo Press quality_controlled: '1' scopus_import: '1' status: public title: Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 41 year: '2022' ... --- _id: '12080' abstract: - lang: eng 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.' 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.' article_number: e202112138 article_processing_charge: No article_type: original author: - first_name: Mariko full_name: Enshoji, Mariko last_name: Enshoji - first_name: Yoshiko full_name: Miyano, Yoshiko last_name: Miyano - first_name: Nao full_name: Yoshida, Nao last_name: Yoshida - first_name: Makoto full_name: Nagano, Makoto last_name: Nagano - first_name: Minami full_name: Watanabe, Minami last_name: Watanabe - first_name: Mayumi full_name: Kunihiro, Mayumi last_name: Kunihiro - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 - first_name: Junko Y. full_name: Toshima, Junko Y. last_name: Toshima - first_name: Jiro full_name: Toshima, Jiro last_name: Toshima citation: 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 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. 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. 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. 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). date_created: 2022-09-11T22:01:54Z date_published: 2022-08-19T00:00:00Z date_updated: 2023-08-03T13:49:07Z day: '19' ddc: - '570' department: - _id: DaSi doi: 10.1083/jcb.202112138 external_id: isi: - '000932770500001' pmid: - '35984332' file: - access_level: open_access checksum: f2e581e66b5cdab9df81b56e850b3eaa content_type: application/pdf creator: dernst date_created: 2023-01-20T09:32:53Z date_updated: 2023-02-21T23:30:39Z embargo: 2023-02-20 file_id: '12321' file_name: 2022_JCB_Enshoji.pdf file_size: 7816875 relation: main_file file_date_updated: 2023-02-21T23:30:39Z has_accepted_license: '1' intvolume: ' 221' isi: 1 issue: '10' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-sa/4.0/ month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Journal of Cell Biology publication_identifier: eissn: - 1540-8140 issn: - 0021-9525 publication_status: published publisher: Rockefeller University Press quality_controlled: '1' scopus_import: '1' status: public title: Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 221 year: '2022' ... --- _id: '10614' abstract: - lang: eng 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. ' acknowledged_ssus: - _id: LifeSc 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.' article_processing_charge: No article_type: original author: - first_name: Vera full_name: Belyaeva, Vera id: 47F080FE-F248-11E8-B48F-1D18A9856A87 last_name: Belyaeva - first_name: Stephanie full_name: Wachner, Stephanie id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87 last_name: Wachner - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Igor full_name: Gridchyn, Igor id: 4B60654C-F248-11E8-B48F-1D18A9856A87 last_name: Gridchyn orcid: 0000-0002-1807-1929 - first_name: Maria full_name: Akhmanova, Maria id: 3425EC26-F248-11E8-B48F-1D18A9856A87 last_name: Akhmanova orcid: 0000-0003-1522-3162 - first_name: M full_name: Linder, M last_name: Linder - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: M full_name: Sibilia, M last_name: Sibilia - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: 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 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 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. 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. 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. 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. date_created: 2022-01-12T10:18:17Z date_published: 2022-01-06T00:00:00Z date_updated: 2024-03-27T23:30:28Z day: '06' ddc: - '570' department: - _id: DaSi - _id: JoCs doi: 10.1371/journal.pbio.3001494 ec_funded: 1 external_id: isi: - '000971223700001' pmid: - '34990456' file: - access_level: open_access checksum: f454212a5522a7818ba4b2892315c478 content_type: application/pdf creator: cchlebak date_created: 2022-01-12T13:50:04Z date_updated: 2022-01-12T13:50:04Z file_id: '10615' file_name: 2022_PLOSBio_Belyaeva.pdf file_size: 5426932 relation: main_file success: 1 file_date_updated: 2022-01-12T13:50:04Z has_accepted_license: '1' intvolume: ' 20' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: e3001494 pmid: 1 project: - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: Drosophila TNFa´s Funktion in Immunzellen - _id: 26199CA4-B435-11E9-9278-68D0E5697425 grant_number: '24800' name: Tissue barrier penetration is crucial for immunity and metastasis - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions publication: PLoS Biology publication_identifier: eissn: - 1545-7885 issn: - 1544-9173 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: link: - relation: earlier_version url: https://www.biorxiv.org/content/10.1101/2020.09.18.301481 - description: News on the ISTA Website relation: press_release url: https://ista.ac.at/en/news/resisting-the-pressure/ record: - id: '8557' relation: earlier_version status: public - id: '11193' relation: dissertation_contains status: public scopus_import: '1' status: public title: Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 20 year: '2022' ... --- _id: '11193' abstract: - lang: eng 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." acknowledged_ssus: - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Stephanie full_name: Wachner, Stephanie id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87 last_name: Wachner citation: 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. ieee: S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells,” Institute of Science and Technology Austria, 2022. ista: Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria. 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. date_created: 2022-04-20T08:59:07Z date_published: 2022-04-20T00:00:00Z date_updated: 2023-09-19T10:15:54Z day: '20' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: DaSi doi: 10.15479/at:ista:11193 file: - access_level: open_access checksum: 999ab16884c4522486136ebc5ae8dbff content_type: application/pdf creator: cchlebak date_created: 2022-04-20T09:03:57Z date_updated: 2023-04-21T22:30:03Z embargo: 2023-04-20 file_id: '11195' file_name: Thesis_Stephanie_Wachner_20200414_formatted.pdf file_size: 8820951 relation: main_file - access_level: closed checksum: fd92b1e38d53bdf8b458213882d41383 content_type: application/x-zip-compressed creator: cchlebak date_created: 2022-04-22T12:41:00Z date_updated: 2023-04-21T22:30:03Z embargo_to: open_access file_id: '11329' file_name: Thesis_Stephanie_Wachner_20200414.zip file_size: 65864612 relation: source_file file_date_updated: 2023-04-21T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '170' project: - _id: 26199CA4-B435-11E9-9278-68D0E5697425 grant_number: '24800' name: Tissue barrier penetration is crucial for immunity and metastasis publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '10614' relation: part_of_dissertation status: public - id: '544' relation: part_of_dissertation status: public status: public supervisor: - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 title: Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2022' ... --- _id: '9363' abstract: - lang: eng 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. 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. article_processing_charge: No author: - first_name: Álvaro full_name: Inglés Prieto, Álvaro id: 2A9DB292-F248-11E8-B48F-1D18A9856A87 last_name: Inglés Prieto orcid: 0000-0002-5409-8571 - first_name: Nikolas full_name: Furthmann, Nikolas last_name: Furthmann - first_name: Samuel H. full_name: Crossman, Samuel H. last_name: Crossman - first_name: Alexandra Madelaine full_name: Tichy, Alexandra Madelaine last_name: Tichy - first_name: Nina full_name: Hoyer, Nina last_name: Hoyer - first_name: Meike full_name: Petersen, Meike last_name: Petersen - first_name: Vanessa full_name: Zheden, Vanessa id: 39C5A68A-F248-11E8-B48F-1D18A9856A87 last_name: Zheden - first_name: Julia full_name: Bicher, Julia id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87 last_name: Bicher - first_name: Eva full_name: Gschaider-Reichhart, Eva id: 3FEE232A-F248-11E8-B48F-1D18A9856A87 last_name: Gschaider-Reichhart orcid: 0000-0002-7218-7738 - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 - first_name: Peter full_name: Soba, Peter last_name: Soba - first_name: Konstanze F. full_name: Winklhofer, Konstanze F. last_name: Winklhofer - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 citation: 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 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 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. 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. 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. 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. 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. date_created: 2021-05-02T22:01:29Z date_published: 2021-04-01T00:00:00Z date_updated: 2023-08-08T13:17:47Z day: '01' ddc: - '570' department: - _id: EM-Fac - _id: LoSw - _id: DaSi doi: 10.1371/journal.pgen.1009479 external_id: isi: - '000640606700001' file: - access_level: open_access checksum: 82a74668f863e8dfb22fdd4f845c92ce content_type: application/pdf creator: kschuh date_created: 2021-05-04T09:05:27Z date_updated: 2021-05-04T09:05:27Z file_id: '9369' file_name: 2021_PLOS_Ingles-Prieto.pdf file_size: 3072764 relation: main_file success: 1 file_date_updated: 2021-05-04T09:05:27Z has_accepted_license: '1' intvolume: ' 17' isi: 1 issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: e1009479 publication: PLoS genetics publication_identifier: eissn: - '15537404' publication_status: published publisher: Public Library of Science quality_controlled: '1' scopus_import: '1' status: public title: Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 17 year: '2021' ...