[{"isi":1,"quality_controlled":"1","project":[{"name":"Investigating the role of transporters in invasive migration through junctions","call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425","grant_number":"334077"},{"name":"Modeling epithelial tissue mechanics during cell invasion","call_identifier":"FWF","grant_number":"M02379","_id":"264CBBAC-B435-11E9-9278-68D0E5697425"},{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen","call_identifier":"FWF"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000771957000001"]},"acknowledged_ssus":[{"_id":"Bio"}],"language":[{"iso":"eng"}],"doi":"10.15252/embj.2021109049","month":"03","publication_identifier":{"eissn":["1460-2075"]},"publication_status":"published","publisher":"Embo Press","department":[{"_id":"DaSi"},{"_id":"LoSw"}],"year":"2022","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_created":"2022-03-24T13:23:09Z","date_updated":"2023-08-03T06:13:14Z","volume":41,"author":[{"orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87","last_name":"Emtenani","first_name":"Shamsi","full_name":"Emtenani, Shamsi"},{"last_name":"Martin","first_name":"Elliot T","full_name":"Martin, Elliot T"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","first_name":"Attila"},{"id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Bicher","full_name":"Bicher, Julia"},{"first_name":"Jakob-Wendelin","last_name":"Genger","full_name":"Genger, Jakob-Wendelin"},{"full_name":"Köcher, Thomas","first_name":"Thomas","last_name":"Köcher"},{"last_name":"Akhmanova","first_name":"Maria","orcid":"0000-0003-1522-3162","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","full_name":"Akhmanova, Maria"},{"first_name":"Mariana","last_name":"Pereira Guarda","id":"6de81d9d-e2f2-11eb-945a-af8bc2a60b26","full_name":"Pereira Guarda, Mariana"},{"full_name":"Roblek, Marko","last_name":"Roblek","first_name":"Marko","orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bergthaler, Andreas","last_name":"Bergthaler","first_name":"Andreas"},{"full_name":"Hurd, Thomas R","last_name":"Hurd","first_name":"Thomas R"},{"full_name":"Rangan, Prashanth","last_name":"Rangan","first_name":"Prashanth"},{"full_name":"Siekhaus, Daria E","last_name":"Siekhaus","first_name":"Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"article_number":"e109049","file_date_updated":"2022-03-24T13:22:41Z","ec_funded":1,"article_type":"original","publication":"The Embo Journal","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","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.","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).","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.","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."},"date_published":"2022-03-23T00:00:00Z","scopus_import":"1","day":"23","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","status":"public","ddc":["570"],"title":"Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila","intvolume":" 41","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10918","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":4344585,"creator":"siekhaus","access_level":"open_access","file_name":"Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosopila.pdf","checksum":"dba48580fe0fefaa4c63078d1d2a35df","date_updated":"2022-03-24T13:22:41Z","date_created":"2022-03-24T13:22:41Z","relation":"main_file","file_id":"10919"}],"type":"journal_article","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."}]},{"language":[{"iso":"eng"}],"doi":"10.1083/jcb.202112138","quality_controlled":"1","isi":1,"external_id":{"isi":["000932770500001"],"pmid":["35984332"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"oa":1,"month":"08","publication_identifier":{"eissn":["1540-8140"],"issn":["0021-9525"]},"date_created":"2022-09-11T22:01:54Z","date_updated":"2023-08-03T13:49:07Z","volume":221,"author":[{"full_name":"Enshoji, Mariko","first_name":"Mariko","last_name":"Enshoji"},{"full_name":"Miyano, Yoshiko","first_name":"Yoshiko","last_name":"Miyano"},{"last_name":"Yoshida","first_name":"Nao","full_name":"Yoshida, Nao"},{"first_name":"Makoto","last_name":"Nagano","full_name":"Nagano, Makoto"},{"full_name":"Watanabe, Minami","first_name":"Minami","last_name":"Watanabe"},{"full_name":"Kunihiro, Mayumi","last_name":"Kunihiro","first_name":"Mayumi"},{"last_name":"Siekhaus","first_name":"Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E"},{"first_name":"Junko Y.","last_name":"Toshima","full_name":"Toshima, Junko Y."},{"full_name":"Toshima, Jiro","first_name":"Jiro","last_name":"Toshima"}],"publication_status":"published","department":[{"_id":"DaSi"}],"publisher":"Rockefeller University Press","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.","year":"2022","pmid":1,"file_date_updated":"2023-02-21T23:30:39Z","article_number":"e202112138","date_published":"2022-08-19T00:00:00Z","article_type":"original","publication":"Journal of Cell Biology","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","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.","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","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.","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).","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.","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."},"day":"19","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","file":[{"checksum":"f2e581e66b5cdab9df81b56e850b3eaa","date_updated":"2023-02-21T23:30:39Z","date_created":"2023-01-20T09:32:53Z","relation":"main_file","file_id":"12321","embargo":"2023-02-20","file_size":7816875,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2022_JCB_Enshoji.pdf"}],"oa_version":"Published Version","title":"Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway","status":"public","ddc":["570"],"intvolume":" 221","_id":"12080","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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."}],"issue":"10","type":"journal_article"},{"pmid":1,"year":"2022","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.","department":[{"_id":"DaSi"},{"_id":"JoCs"}],"publisher":"Public Library of Science","publication_status":"published","related_material":{"record":[{"id":"8557","relation":"earlier_version","status":"public"},{"id":"11193","relation":"dissertation_contains","status":"public"}],"link":[{"relation":"earlier_version","url":"https://www.biorxiv.org/content/10.1101/2020.09.18.301481"},{"url":"https://ista.ac.at/en/news/resisting-the-pressure/","relation":"press_release","description":"News on the ISTA Website"}]},"author":[{"full_name":"Belyaeva, Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87","last_name":"Belyaeva","first_name":"Vera"},{"full_name":"Wachner, Stephanie","first_name":"Stephanie","last_name":"Wachner","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87"},{"id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","first_name":"Attila","last_name":"György","full_name":"György, Attila"},{"full_name":"Emtenani, Shamsi","last_name":"Emtenani","first_name":"Shamsi","orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Gridchyn","first_name":"Igor","orcid":"0000-0002-1807-1929","id":"4B60654C-F248-11E8-B48F-1D18A9856A87","full_name":"Gridchyn, Igor"},{"full_name":"Akhmanova, Maria","first_name":"Maria","last_name":"Akhmanova","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1522-3162"},{"full_name":"Linder, M","first_name":"M","last_name":"Linder"},{"last_name":"Roblek","first_name":"Marko","orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87","full_name":"Roblek, Marko"},{"full_name":"Sibilia, M","first_name":"M","last_name":"Sibilia"},{"orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E","full_name":"Siekhaus, Daria E"}],"volume":20,"date_updated":"2024-03-28T23:30:29Z","date_created":"2022-01-12T10:18:17Z","ec_funded":1,"file_date_updated":"2022-01-12T13:50:04Z","external_id":{"pmid":["34990456"],"isi":["000971223700001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"project":[{"call_identifier":"FWF","name":"Drosophila TNFa´s Funktion in Immunzellen","_id":"253B6E48-B435-11E9-9278-68D0E5697425","grant_number":"P29638"},{"_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","call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425","grant_number":"334077"}],"quality_controlled":"1","isi":1,"doi":"10.1371/journal.pbio.3001494","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"publication_identifier":{"issn":["1544-9173"],"eissn":["1545-7885"]},"month":"01","_id":"10614","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 20","title":"Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila","ddc":["570"],"status":"public","file":[{"access_level":"open_access","file_name":"2022_PLOSBio_Belyaeva.pdf","creator":"cchlebak","content_type":"application/pdf","file_size":5426932,"file_id":"10615","relation":"main_file","success":1,"checksum":"f454212a5522a7818ba4b2892315c478","date_updated":"2022-01-12T13:50:04Z","date_created":"2022-01-12T13:50:04Z"}],"oa_version":"Published Version","type":"journal_article","issue":"1","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. "}],"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.","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.","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.","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","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.","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"},"publication":"PLoS Biology","page":"e3001494","article_type":"original","date_published":"2022-01-06T00:00:00Z","scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"06"},{"date_updated":"2023-09-19T10:15:54Z","date_created":"2022-04-20T08:59:07Z","related_material":{"record":[{"id":"10614","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"544"}]},"author":[{"id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","last_name":"Wachner","first_name":"Stephanie","full_name":"Wachner, Stephanie"}],"department":[{"_id":"GradSch"},{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","publication_status":"published","year":"2022","file_date_updated":"2023-04-21T22:30:03Z","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"supervisor":[{"full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E"}],"degree_awarded":"PhD","doi":"10.15479/at:ista:11193","project":[{"name":"Tissue barrier penetration is crucial for immunity and metastasis","grant_number":"24800","_id":"26199CA4-B435-11E9-9278-68D0E5697425"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"publication_identifier":{"issn":["2663-337X"]},"month":"04","oa_version":"Published Version","file":[{"file_id":"11195","embargo":"2023-04-20","relation":"main_file","date_created":"2022-04-20T09:03:57Z","date_updated":"2023-04-21T22:30:03Z","checksum":"999ab16884c4522486136ebc5ae8dbff","file_name":"Thesis_Stephanie_Wachner_20200414_formatted.pdf","access_level":"open_access","creator":"cchlebak","content_type":"application/pdf","file_size":8820951},{"file_size":65864612,"content_type":"application/x-zip-compressed","creator":"cchlebak","embargo_to":"open_access","file_name":"Thesis_Stephanie_Wachner_20200414.zip","access_level":"closed","date_created":"2022-04-22T12:41:00Z","date_updated":"2023-04-21T22:30:03Z","checksum":"fd92b1e38d53bdf8b458213882d41383","relation":"source_file","file_id":"11329"}],"title":"Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells","status":"public","ddc":["570"],"_id":"11193","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","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"}],"alternative_title":["ISTA Thesis"],"type":"dissertation","date_published":"2022-04-20T00:00:00Z","page":"170","citation":{"ista":"Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria.","ieee":"S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells,” Institute of Science and Technology Austria, 2022.","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","ama":"Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. 2022. doi: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.","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."},"has_accepted_license":"1","article_processing_charge":"No","day":"20"},{"page":"e1009479","publication":"PLoS genetics","citation":{"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.","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.","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.","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","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.","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"},"date_published":"2021-04-01T00:00:00Z","scopus_import":"1","day":"01","has_accepted_license":"1","article_processing_charge":"No","status":"public","title":"Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease","ddc":["570"],"intvolume":" 17","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9363","file":[{"file_size":3072764,"content_type":"application/pdf","creator":"kschuh","file_name":"2021_PLOS_Ingles-Prieto.pdf","access_level":"open_access","date_created":"2021-05-04T09:05:27Z","date_updated":"2021-05-04T09:05:27Z","checksum":"82a74668f863e8dfb22fdd4f845c92ce","success":1,"relation":"main_file","file_id":"9369"}],"oa_version":"Published Version","type":"journal_article","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."}],"issue":"4","quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000640606700001"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1371/journal.pgen.1009479","month":"04","publication_identifier":{"eissn":["15537404"]},"publication_status":"published","department":[{"_id":"EM-Fac"},{"_id":"LoSw"},{"_id":"DaSi"}],"publisher":"Public Library of Science","year":"2021","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.","date_updated":"2023-08-08T13:17:47Z","date_created":"2021-05-02T22:01:29Z","volume":17,"author":[{"full_name":"Inglés Prieto, Álvaro","last_name":"Inglés Prieto","first_name":"Álvaro","orcid":"0000-0002-5409-8571","id":"2A9DB292-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Nikolas","last_name":"Furthmann","full_name":"Furthmann, Nikolas"},{"full_name":"Crossman, Samuel H.","first_name":"Samuel H.","last_name":"Crossman"},{"last_name":"Tichy","first_name":"Alexandra Madelaine","full_name":"Tichy, Alexandra Madelaine"},{"full_name":"Hoyer, Nina","first_name":"Nina","last_name":"Hoyer"},{"full_name":"Petersen, Meike","last_name":"Petersen","first_name":"Meike"},{"last_name":"Zheden","first_name":"Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","full_name":"Zheden, Vanessa"},{"full_name":"Bicher, Julia","first_name":"Julia","last_name":"Bicher","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gschaider-Reichhart, Eva","orcid":"0000-0002-7218-7738","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","last_name":"Gschaider-Reichhart","first_name":"Eva"},{"first_name":"Attila","last_name":"György","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","full_name":"György, Attila"},{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","first_name":"Daria E","last_name":"Siekhaus","full_name":"Siekhaus, Daria E"},{"full_name":"Soba, Peter","last_name":"Soba","first_name":"Peter"},{"last_name":"Winklhofer","first_name":"Konstanze F.","full_name":"Winklhofer, Konstanze F."},{"first_name":"Harald L","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L"}],"file_date_updated":"2021-05-04T09:05:27Z"}]