[{"year":"2018","publication_status":"published","publisher":"Springer Nature","department":[{"_id":"HaJa"},{"_id":"CaGu"},{"_id":"MiSi"}],"author":[{"id":"4863116E-F248-11E8-B48F-1D18A9856A87","last_name":"Morri","first_name":"Maurizio","full_name":"Morri, Maurizio"},{"id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87","last_name":"Sanchez-Romero","first_name":"Inmaculada","full_name":"Sanchez-Romero, Inmaculada"},{"full_name":"Tichy, Alexandra-Madelaine","last_name":"Tichy","first_name":"Alexandra-Madelaine","id":"29D8BB2C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kainrath, Stephanie","last_name":"Kainrath","first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gerrard, Elliot J.","first_name":"Elliot J.","last_name":"Gerrard"},{"full_name":"Hirschfeld, Priscila","id":"435ACB3A-F248-11E8-B48F-1D18A9856A87","last_name":"Hirschfeld","first_name":"Priscila"},{"full_name":"Schwarz, Jan","last_name":"Schwarz","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","last_name":"Janovjak","first_name":"Harald L"}],"date_updated":"2023-09-19T14:29:32Z","date_created":"2019-02-14T10:50:24Z","volume":9,"article_number":"1950","file_date_updated":"2020-07-14T12:47:14Z","ec_funded":1,"external_id":{"isi":["000432280000006"]},"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,"isi":1,"quality_controlled":"1","project":[{"name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7","grant_number":"303564","_id":"25548C20-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"255A6082-B435-11E9-9278-68D0E5697425"}],"doi":"10.1038/s41467-018-04342-1","language":[{"iso":"eng"}],"month":"12","publication_identifier":{"issn":["2041-1723"]},"_id":"5984","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"title":"Optical functionalization of human class A orphan G-protein-coupled receptors","status":"public","intvolume":" 9","file":[{"relation":"main_file","file_id":"5985","checksum":"8325fcc194264af4749e662a73bf66b5","date_created":"2019-02-14T10:58:29Z","date_updated":"2020-07-14T12:47:14Z","access_level":"open_access","file_name":"2018_Springer_Morri.pdf","content_type":"application/pdf","file_size":1349914,"creator":"kschuh"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs.","lang":"eng"}],"issue":"1","publication":"Nature Communications","citation":{"chicago":"Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-04342-1.","short":"M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld, J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018).","mla":"Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications, vol. 9, no. 1, 1950, Springer Nature, 2018, doi:10.1038/s41467-018-04342-1.","apa":"Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J., Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-018-04342-1","ieee":"M. Morri et al., “Optical functionalization of human class A orphan G-protein-coupled receptors,” Nature Communications, vol. 9, no. 1. Springer Nature, 2018.","ista":"Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P, Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 9(1), 1950.","ama":"Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-04342-1"},"date_published":"2018-12-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"No","has_accepted_license":"1"},{"date_published":"2018-11-01T00:00:00Z","publication":"Molecular Biology of the Cell","citation":{"ieee":"S. Dolati et al., “On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility,” Molecular Biology of the Cell, vol. 29, no. 22. American Society for Cell Biology , pp. 2674–2686, 2018.","apa":"Dolati, S., Kage, F., Mueller, J., Müsken, M., Kirchner, M., Dittmar, G., … Falcke, M. (2018). On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell. American Society for Cell Biology . https://doi.org/10.1091/mbc.e18-02-0082","ista":"Dolati S, Kage F, Mueller J, Müsken M, Kirchner M, Dittmar G, Sixt MK, Rottner K, Falcke M. 2018. On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell. 29(22), 2674–2686.","ama":"Dolati S, Kage F, Mueller J, et al. On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell. 2018;29(22):2674-2686. doi:10.1091/mbc.e18-02-0082","chicago":"Dolati, Setareh, Frieda Kage, Jan Mueller, Mathias Müsken, Marieluise Kirchner, Gunnar Dittmar, Michael K Sixt, Klemens Rottner, and Martin Falcke. “On the Relation between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal Cell Motility.” Molecular Biology of the Cell. American Society for Cell Biology , 2018. https://doi.org/10.1091/mbc.e18-02-0082.","short":"S. Dolati, F. Kage, J. Mueller, M. Müsken, M. Kirchner, G. Dittmar, M.K. Sixt, K. Rottner, M. Falcke, Molecular Biology of the Cell 29 (2018) 2674–2686.","mla":"Dolati, Setareh, et al. “On the Relation between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal Cell Motility.” Molecular Biology of the Cell, vol. 29, no. 22, American Society for Cell Biology , 2018, pp. 2674–86, doi:10.1091/mbc.e18-02-0082."},"page":"2674-2686","day":"01","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","oa_version":"Published Version","file":[{"file_name":"2018_ASCB_Dolati.pdf","access_level":"open_access","content_type":"application/pdf","file_size":6668971,"creator":"kschuh","relation":"main_file","file_id":"5994","date_updated":"2020-07-14T12:47:15Z","date_created":"2019-02-14T12:34:29Z","checksum":"e98465b4416b3e804c47f40086932af2"}],"_id":"5992","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","title":"On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility","ddc":["570"],"intvolume":" 29","abstract":[{"text":"Lamellipodia are flat membrane protrusions formed during mesenchymal motion. Polymerization at the leading edge assembles the actin filament network and generates protrusion force. How this force is supported by the network and how the assembly rate is shared between protrusion and network retrograde flow determines the protrusion rate. We use mathematical modeling to understand experiments changing the F-actin density in lamellipodia of B16-F1 melanoma cells by modulation of Arp2/3 complex activity or knockout of the formins FMNL2 and FMNL3. Cells respond to a reduction of density with a decrease of protrusion velocity, an increase in the ratio of force to filament number, but constant network assembly rate. The relation between protrusion force and tension gradient in the F-actin network and the density dependency of friction, elasticity, and viscosity of the network explain the experimental observations. The formins act as filament nucleators and elongators with differential rates. Modulation of their activity suggests an effect on network assembly rate. Contrary to these expectations, the effect of changes in elongator composition is much weaker than the consequences of the density change. We conclude that the force acting on the leading edge membrane is the force required to drive F-actin network retrograde flow.","lang":"eng"}],"issue":"22","type":"journal_article","doi":"10.1091/mbc.e18-02-0082","language":[{"iso":"eng"}],"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)"},"external_id":{"pmid":["30156465"],"isi":["000455641000011"]},"oa":1,"isi":1,"quality_controlled":"1","month":"11","publication_identifier":{"eissn":["1939-4586"]},"author":[{"full_name":"Dolati, Setareh","last_name":"Dolati","first_name":"Setareh"},{"full_name":"Kage, Frieda","first_name":"Frieda","last_name":"Kage"},{"first_name":"Jan","last_name":"Mueller","full_name":"Mueller, Jan"},{"full_name":"Müsken, Mathias","last_name":"Müsken","first_name":"Mathias"},{"first_name":"Marieluise","last_name":"Kirchner","full_name":"Kirchner, Marieluise"},{"full_name":"Dittmar, Gunnar","first_name":"Gunnar","last_name":"Dittmar"},{"first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"},{"full_name":"Rottner, Klemens","first_name":"Klemens","last_name":"Rottner"},{"last_name":"Falcke","first_name":"Martin","full_name":"Falcke, Martin"}],"date_created":"2019-02-14T12:25:47Z","date_updated":"2023-09-19T14:30:23Z","volume":29,"year":"2018","pmid":1,"publication_status":"published","department":[{"_id":"MiSi"}],"publisher":"American Society for Cell Biology ","file_date_updated":"2020-07-14T12:47:15Z","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/"},{"publication":"The Journal of Experimental Medicine","citation":{"ama":"Moalli F, Ficht X, Germann P, et al. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. 2018;2015(7):1869–1890. doi:10.1084/jem.20170896","ista":"Moalli F, Ficht X, Germann P, Vladymyrov M, Stolp B, de Vries I, Lyck R, Balmer J, Fiocchi A, Kreutzfeldt M, Merkler D, Iannacone M, Ariga A, Stoffel MH, Sharpe J, Bähler M, Sixt MK, Diz-Muñoz A, Stein JV. 2018. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. 2015(7), 1869–1890.","ieee":"F. Moalli et al., “The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells,” The Journal of Experimental Medicine, vol. 2015, no. 7. Rockefeller University Press, pp. 1869–1890, 2018.","apa":"Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., de Vries, I., … Stein, J. V. (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. Rockefeller University Press. https://doi.org/10.1084/jem.20170896","mla":"Moalli, Federica, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” The Journal of Experimental Medicine, vol. 2015, no. 7, Rockefeller University Press, 2018, pp. 1869–1890, doi:10.1084/jem.20170896.","short":"F. Moalli, X. Ficht, P. Germann, M. Vladymyrov, B. Stolp, I. de Vries, R. Lyck, J. Balmer, A. Fiocchi, M. Kreutzfeldt, D. Merkler, M. Iannacone, A. Ariga, M.H. Stoffel, J. Sharpe, M. Bähler, M.K. Sixt, A. Diz-Muñoz, J.V. Stein, The Journal of Experimental Medicine 2015 (2018) 1869–1890.","chicago":"Moalli, Federica, Xenia Ficht, Philipp Germann, Mykhailo Vladymyrov, Bettina Stolp, Ingrid de Vries, Ruth Lyck, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” The Journal of Experimental Medicine. Rockefeller University Press, 2018. https://doi.org/10.1084/jem.20170896."},"page":"1869–1890","date_published":"2018-06-06T00:00:00Z","scopus_import":"1","day":"06","has_accepted_license":"1","article_processing_charge":"No","_id":"6497","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","title":"The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells","ddc":["570"],"intvolume":" 2015","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2018_rupress_Moalli.pdf","creator":"kschuh","content_type":"application/pdf","file_size":3841660,"file_id":"6498","relation":"main_file","checksum":"86ae5331f9bfced9a6358a790a04bef4","date_created":"2019-05-28T12:40:05Z","date_updated":"2020-07-14T12:47:32Z"}],"type":"journal_article","abstract":[{"text":"T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/− CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations.","lang":"eng"}],"issue":"7","oa":1,"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)"},"external_id":{"isi":["000440822900011"]},"quality_controlled":"1","isi":1,"doi":"10.1084/jem.20170896","language":[{"iso":"eng"}],"month":"06","publication_identifier":{"eissn":["1540-9538"],"issn":["0022-1007"]},"year":"2018","publication_status":"published","department":[{"_id":"MiSi"}],"publisher":"Rockefeller University Press","author":[{"first_name":"Federica","last_name":"Moalli","full_name":"Moalli, Federica"},{"full_name":"Ficht, Xenia","last_name":"Ficht","first_name":"Xenia"},{"full_name":"Germann, Philipp","last_name":"Germann","first_name":"Philipp"},{"first_name":"Mykhailo","last_name":"Vladymyrov","full_name":"Vladymyrov, Mykhailo"},{"last_name":"Stolp","first_name":"Bettina","full_name":"Stolp, Bettina"},{"full_name":"de Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"de Vries"},{"first_name":"Ruth","last_name":"Lyck","full_name":"Lyck, Ruth"},{"full_name":"Balmer, Jasmin","last_name":"Balmer","first_name":"Jasmin"},{"first_name":"Amleto","last_name":"Fiocchi","full_name":"Fiocchi, Amleto"},{"full_name":"Kreutzfeldt, Mario","last_name":"Kreutzfeldt","first_name":"Mario"},{"full_name":"Merkler, Doron","first_name":"Doron","last_name":"Merkler"},{"last_name":"Iannacone","first_name":"Matteo","full_name":"Iannacone, Matteo"},{"last_name":"Ariga","first_name":"Akitaka","full_name":"Ariga, Akitaka"},{"full_name":"Stoffel, Michael H.","last_name":"Stoffel","first_name":"Michael H."},{"first_name":"James","last_name":"Sharpe","full_name":"Sharpe, James"},{"first_name":"Martin","last_name":"Bähler","full_name":"Bähler, Martin"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K"},{"full_name":"Diz-Muñoz, Alba","last_name":"Diz-Muñoz","first_name":"Alba"},{"first_name":"Jens V.","last_name":"Stein","full_name":"Stein, Jens V."}],"date_created":"2019-05-28T12:36:47Z","date_updated":"2023-09-19T14:52:08Z","volume":2015,"file_date_updated":"2020-07-14T12:47:32Z"},{"abstract":[{"lang":"eng","text":"During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined."}],"issue":"6382","type":"journal_article","oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"402","title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice","status":"public","intvolume":" 359","day":"23","article_processing_charge":"No","scopus_import":"1","date_published":"2018-03-23T00:00:00Z","publication":"Science","citation":{"ama":"Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 2018;359(6382):1408-1411. doi:10.1126/science.aal3662","apa":"Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G., … Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aal3662","ieee":"M. Brown et al., “Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice,” Science, vol. 359, no. 6382. American Association for the Advancement of Science, pp. 1408–1411, 2018.","ista":"Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382), 1408–1411.","short":"M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z. Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018) 1408–1411.","mla":"Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” Science, vol. 359, no. 6382, American Association for the Advancement of Science, 2018, pp. 1408–11, doi:10.1126/science.aal3662.","chicago":"Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner, Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” Science. American Association for the Advancement of Science, 2018. https://doi.org/10.1126/science.aal3662."},"article_type":"original","page":"1408 - 1411","ec_funded":1,"publist_id":"7428","author":[{"id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus"},{"full_name":"Assen, Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119","first_name":"Frank P","last_name":"Assen"},{"full_name":"Leithner, Alexander F","first_name":"Alexander F","last_name":"Leithner","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X"},{"first_name":"Jun","last_name":"Abe","full_name":"Abe, Jun"},{"full_name":"Schachner, Helga","first_name":"Helga","last_name":"Schachner"},{"full_name":"Asfour, Gabriele","last_name":"Asfour","first_name":"Gabriele"},{"full_name":"Bagó Horváth, Zsuzsanna","last_name":"Bagó Horváth","first_name":"Zsuzsanna"},{"full_name":"Stein, Jens","last_name":"Stein","first_name":"Jens"},{"full_name":"Uhrin, Pavel","last_name":"Uhrin","first_name":"Pavel"},{"first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"},{"full_name":"Kerjaschki, Dontscho","first_name":"Dontscho","last_name":"Kerjaschki"}],"related_material":{"record":[{"id":"6947","status":"public","relation":"dissertation_contains"}]},"date_created":"2018-12-11T11:46:16Z","date_updated":"2024-03-28T23:30:09Z","volume":359,"year":"2018","acknowledgement":"M.B. was supported by the Cell Communication in Health and Disease graduate study program of the Austrian Science Fund (FWF) and the Medical University of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556) and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging, the Sixt lab for intellectual input, M. Schunn for help with the design of the in vivo experiments, F. Langer for technical assistance with the in vivo experiments, the bioimaging facility of IST Austria for support, and R. Efferl for providing the CT26 cell line.","pmid":1,"publication_status":"published","department":[{"_id":"MiSi"}],"publisher":"American Association for the Advancement of Science","month":"03","doi":"10.1126/science.aal3662","acknowledged_ssus":[{"_id":"Bio"}],"language":[{"iso":"eng"}],"oa":1,"external_id":{"isi":["000428043600047"],"pmid":["29567714"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1126/science.aal3662"}],"quality_controlled":"1","isi":1,"project":[{"_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","call_identifier":"FWF"},{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"}]},{"abstract":[{"lang":"eng","text":"In the here presented thesis, we explore the role of branched actin networks in cell migration and antigen presentation, the two most relevant processes in dendritic cell biology. Branched actin networks construct lamellipodial protrusions at the leading edge of migrating cells. These are typically seen as adhesive structures, which mediate force transduction to the extracellular matrix that leads to forward locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found that the resulting cells lack lamellipodial protrusions. Instead, depending on the maturation state, one or multiple filopodia were formed. By challenging these cells in a variety of migration assays we found that lamellipodial protrusions are dispensable for the locomotion of leukocytes and actually dampen the speed of migration. However, lamellipodia are critically required to negotiate complex environments that DCs experience while they travel to the next draining lymph node. Taken together our results suggest that leukocyte lamellipodia have rather a sensory- than a force transducing function. Furthermore, we show for the first time structure and dynamics of dendritic cell F-actin at the immunological synapse with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension, leading to an altered ultrastructure of the immunological synapse and severe T cell priming defects. These results point towards a previously unappreciated role of the cellular mechanics of dendritic cells in T cell activation. Additionally, we present a novel cell culture based system for the differentiation of dendritic cells from conditionally immortalized hematopoietic precursors. These precursor cells are genetically tractable via the CRISPR/Cas9 system while they retain their ability to differentiate into highly migratory dendritic cells and other immune cells. This will foster the study of all aspects of dendritic cell biology and beyond. "}],"alternative_title":["ISTA Thesis"],"type":"dissertation","file":[{"relation":"source_file","file_id":"6219","checksum":"d5e3edbac548c26c1fa43a4b37a54a4c","date_created":"2019-04-05T09:23:11Z","date_updated":"2021-02-11T23:30:17Z","access_level":"closed","embargo_to":"open_access","file_name":"PhD_thesis_AlexLeithner_final_version.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":29027671,"creator":"dernst"},{"relation":"main_file","embargo":"2019-04-15","file_id":"6220","date_created":"2019-04-05T09:23:11Z","date_updated":"2021-02-11T11:17:16Z","checksum":"071f7476db29e41146824ebd0697cb10","file_name":"PhD_thesis_AlexLeithner.pdf","access_level":"open_access","file_size":66045341,"content_type":"application/pdf","creator":"dernst"}],"oa_version":"Published Version","pubrep_id":"998","status":"public","ddc":["571","599","610"],"title":"Branched actin networks in dendritic cell biology","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"323","article_processing_charge":"No","has_accepted_license":"1","day":"12","date_published":"2018-04-12T00:00:00Z","page":"99","citation":{"chicago":"Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_998.","mla":"Leithner, Alexander F. Branched Actin Networks in Dendritic Cell Biology. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_998.","short":"A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute of Science and Technology Austria, 2018.","ista":"Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute of Science and Technology Austria.","apa":"Leithner, A. F. (2018). Branched actin networks in dendritic cell biology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_998","ieee":"A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute of Science and Technology Austria, 2018.","ama":"Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:10.15479/AT:ISTA:th_998"},"publist_id":"7542","file_date_updated":"2021-02-11T23:30:17Z","date_updated":"2023-09-07T12:39:44Z","date_created":"2018-12-11T11:45:49Z","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"1321"}]},"author":[{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Institute of Science and Technology Austria","department":[{"_id":"MiSi"}],"publication_status":"published","year":"2018","acknowledgement":"First of all I would like to thank Michael Sixt for giving me the opportunity to work in \r\nhis group and for his support throughout the years. He is a truly inspiring person and \r\nthe best boss one can imagine. I would also like to thank all current and past \r\nmembers of the Sixt group for their help and the great working atmosphere in the lab. \r\nIt is a true privilege to work with such a bright, funny and friendly group of people and \r\nI’m proud that I could be part of it. Furthermore, I would like to say ‘thank you’ to Daria Siekhaus for all the meetings and discussion we had throughout the years \r\nand to Federica Benvenuti for being part of my committee. I am also grateful to Jack \r\nMerrin in the nanofabrication facility and all the people working in the bioimaging-\r\n, the electron microscopy- and the preclinical facilities.","publication_identifier":{"issn":["2663-337X"]},"month":"04","language":[{"iso":"eng"}],"supervisor":[{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"degree_awarded":"PhD","acknowledged_ssus":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"doi":"10.15479/AT:ISTA:th_998","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},{"title":"Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells","status":"public","intvolume":" 19","_id":"15","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","type":"journal_article","abstract":[{"text":"Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux.","lang":"eng"}],"issue":"6","page":"606 - 616","publication":"Nature Immunology","citation":{"ieee":"M. Hons et al., “Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells,” Nature Immunology, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018.","apa":"Hons, M., Kopf, A., Hauschild, R., Leithner, A. F., Gärtner, F. R., Abe, J., … Sixt, M. K. (2018). Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/s41590-018-0109-z","ista":"Hons M, Kopf A, Hauschild R, Leithner AF, Gärtner FR, Abe J, Renkawitz J, Stein J, Sixt MK. 2018. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 19(6), 606–616.","ama":"Hons M, Kopf A, Hauschild R, et al. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 2018;19(6):606-616. doi:10.1038/s41590-018-0109-z","chicago":"Hons, Miroslav, Aglaja Kopf, Robert Hauschild, Alexander F Leithner, Florian R Gärtner, Jun Abe, Jörg Renkawitz, Jens Stein, and Michael K Sixt. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology. Nature Publishing Group, 2018. https://doi.org/10.1038/s41590-018-0109-z.","short":"M. Hons, A. Kopf, R. Hauschild, A.F. Leithner, F.R. Gärtner, J. Abe, J. Renkawitz, J. Stein, M.K. Sixt, Nature Immunology 19 (2018) 606–616.","mla":"Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology, vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:10.1038/s41590-018-0109-z."},"date_published":"2018-05-18T00:00:00Z","scopus_import":"1","day":"18","article_processing_charge":"No","publication_status":"published","department":[{"_id":"MiSi"},{"_id":"Bio"}],"publisher":"Nature Publishing Group","year":"2018","acknowledgement":"This work was funded by grants from the European Research Council (ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S. and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457 and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014).","pmid":1,"date_updated":"2024-03-28T23:30:40Z","date_created":"2018-12-11T11:44:10Z","volume":19,"author":[{"full_name":"Hons, Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","first_name":"Miroslav","last_name":"Hons"},{"orcid":"0000-0002-2187-6656","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","last_name":"Kopf","first_name":"Aglaja","full_name":"Kopf, Aglaja"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","first_name":"Alexander F","last_name":"Leithner"},{"full_name":"Gärtner, Florian R","last_name":"Gärtner","first_name":"Florian R","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jun","last_name":"Abe","full_name":"Abe, Jun"},{"id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369","first_name":"Jörg","last_name":"Renkawitz","full_name":"Renkawitz, Jörg"},{"last_name":"Stein","first_name":"Jens","full_name":"Stein, Jens"},{"last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"related_material":{"record":[{"id":"6891","status":"public","relation":"dissertation_contains"}]},"publist_id":"8040","ec_funded":1,"isi":1,"quality_controlled":"1","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular navigation along spatial gradients","call_identifier":"H2020"},{"name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020","grant_number":"747687","_id":"260AA4E2-B435-11E9-9278-68D0E5697425"},{"name":"Molecular and system level view of immune cell migration","_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014"},{"call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425"}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/29777221","open_access":"1"}],"external_id":{"isi":["000433041500026"],"pmid":["29777221"]},"oa":1,"acknowledged_ssus":[{"_id":"SSU"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41590-018-0109-z","month":"05"},{"doi":"10.7554/eLife.30867","language":[{"iso":"eng"}],"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,"quality_controlled":"1","month":"11","publication_identifier":{"issn":["2050084X"]},"author":[{"first_name":"Felix","last_name":"Spira","full_name":"Spira, Felix"},{"first_name":"Sara","last_name":"Cuylen Haering","full_name":"Cuylen Haering, Sara"},{"first_name":"Shalin","last_name":"Mehta","full_name":"Mehta, Shalin"},{"last_name":"Samwer","first_name":"Matthias","full_name":"Samwer, Matthias"},{"orcid":"0000-0003-0666-8928","id":"35B76592-F248-11E8-B48F-1D18A9856A87","last_name":"Reversat","first_name":"Anne","full_name":"Reversat, Anne"},{"first_name":"Amitabh","last_name":"Verma","full_name":"Verma, Amitabh"},{"first_name":"Rudolf","last_name":"Oldenbourg","full_name":"Oldenbourg, Rudolf"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt"},{"full_name":"Gerlich, Daniel","last_name":"Gerlich","first_name":"Daniel"}],"date_updated":"2023-02-23T12:30:29Z","date_created":"2018-12-11T11:47:14Z","volume":6,"year":"2017","publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"MiSi"}],"file_date_updated":"2020-07-14T12:47:10Z","publist_id":"7245","article_number":"e30867","date_published":"2017-11-06T00:00:00Z","publication":"eLife","citation":{"mla":"Spira, Felix, et al. “Cytokinesis in Vertebrate Cells Initiates by Contraction of an Equatorial Actomyosin Network Composed of Randomly Oriented Filaments.” ELife, vol. 6, e30867, eLife Sciences Publications, 2017, doi:10.7554/eLife.30867.","short":"F. Spira, S. Cuylen Haering, S. Mehta, M. Samwer, A. Reversat, A. Verma, R. Oldenbourg, M.K. Sixt, D. Gerlich, ELife 6 (2017).","chicago":"Spira, Felix, Sara Cuylen Haering, Shalin Mehta, Matthias Samwer, Anne Reversat, Amitabh Verma, Rudolf Oldenbourg, Michael K Sixt, and Daniel Gerlich. “Cytokinesis in Vertebrate Cells Initiates by Contraction of an Equatorial Actomyosin Network Composed of Randomly Oriented Filaments.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.30867.","ama":"Spira F, Cuylen Haering S, Mehta S, et al. Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. eLife. 2017;6. doi:10.7554/eLife.30867","ista":"Spira F, Cuylen Haering S, Mehta S, Samwer M, Reversat A, Verma A, Oldenbourg R, Sixt MK, Gerlich D. 2017. Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. eLife. 6, e30867.","apa":"Spira, F., Cuylen Haering, S., Mehta, S., Samwer, M., Reversat, A., Verma, A., … Gerlich, D. (2017). Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.30867","ieee":"F. Spira et al., “Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments,” eLife, vol. 6. eLife Sciences Publications, 2017."},"day":"06","has_accepted_license":"1","scopus_import":1,"pubrep_id":"919","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"4829","date_created":"2018-12-12T10:10:40Z","date_updated":"2020-07-14T12:47:10Z","checksum":"ba09c1451153d39e4f4b7cee013e314c","file_name":"IST-2017-919-v1+1_elife-30867-figures-v1.pdf","access_level":"open_access","content_type":"application/pdf","file_size":9666973,"creator":"system"},{"checksum":"01eb51f1d6ad679947415a51c988e137","date_updated":"2020-07-14T12:47:10Z","date_created":"2018-12-12T10:10:41Z","relation":"main_file","file_id":"4830","file_size":5951246,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2017-919-v1+2_elife-30867-v1.pdf"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"569","title":"Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments","ddc":["570"],"status":"public","intvolume":" 6","abstract":[{"text":"The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. This strictly depended on myosin II activity, suggesting local network reorganization by mechanical forces. Cortical laser microsurgery revealed that during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. Our data suggest that an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings.","lang":"eng"}],"type":"journal_article"},{"page":"1368 - 1382","citation":{"chicago":"Gärtner, Florian R, Zerkah Ahmad, Gerhild Rosenberger, Shuxia Fan, Leo Nicolai, Benjamin Busch, Gökce Yavuz, et al. “Migrating Platelets Are Mechano Scavengers That Collect and Bundle Bacteria.” Cell Press. Cell Press, 2017. https://doi.org/10.1016/j.cell.2017.11.001.","short":"F.R. Gärtner, Z. Ahmad, G. Rosenberger, S. Fan, L. Nicolai, B. Busch, G. Yavuz, M. Luckner, H. Ishikawa Ankerhold, R. Hennel, A. Benechet, M. Lorenz, S. Chandraratne, I. Schubert, S. Helmer, B. Striednig, K. Stark, M. Janko, R. Böttcher, A. Verschoor, C. Leon, C. Gachet, T. Gudermann, M. Mederos Y Schnitzler, Z. Pincus, M. Iannacone, R. Haas, G. Wanner, K. Lauber, M.K. Sixt, S. Massberg, Cell Press 171 (2017) 1368–1382.","mla":"Gärtner, Florian R., et al. “Migrating Platelets Are Mechano Scavengers That Collect and Bundle Bacteria.” Cell Press, vol. 171, no. 6, Cell Press, 2017, pp. 1368–82, doi:10.1016/j.cell.2017.11.001.","apa":"Gärtner, F. R., Ahmad, Z., Rosenberger, G., Fan, S., Nicolai, L., Busch, B., … Massberg, S. (2017). Migrating platelets are mechano scavengers that collect and bundle bacteria. Cell Press. Cell Press. https://doi.org/10.1016/j.cell.2017.11.001","ieee":"F. R. Gärtner et al., “Migrating platelets are mechano scavengers that collect and bundle bacteria,” Cell Press, vol. 171, no. 6. Cell Press, pp. 1368–1382, 2017.","ista":"Gärtner FR, Ahmad Z, Rosenberger G, Fan S, Nicolai L, Busch B, Yavuz G, Luckner M, Ishikawa Ankerhold H, Hennel R, Benechet A, Lorenz M, Chandraratne S, Schubert I, Helmer S, Striednig B, Stark K, Janko M, Böttcher R, Verschoor A, Leon C, Gachet C, Gudermann T, Mederos Y Schnitzler M, Pincus Z, Iannacone M, Haas R, Wanner G, Lauber K, Sixt MK, Massberg S. 2017. Migrating platelets are mechano scavengers that collect and bundle bacteria. Cell Press. 171(6), 1368–1382.","ama":"Gärtner FR, Ahmad Z, Rosenberger G, et al. Migrating platelets are mechano scavengers that collect and bundle bacteria. Cell Press. 2017;171(6):1368-1382. doi:10.1016/j.cell.2017.11.001"},"publication":"Cell Press","date_published":"2017-11-30T00:00:00Z","scopus_import":1,"day":"30","intvolume":" 171","status":"public","title":"Migrating platelets are mechano scavengers that collect and bundle bacteria","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"571","oa_version":"None","type":"journal_article","issue":"6","abstract":[{"lang":"eng","text":"Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection. In addition to their role in thrombosis and hemostasis, platelets can also migrate to sites of infection to help trap bacteria and clear the vascular surface."}],"project":[{"grant_number":"747687","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020"}],"quality_controlled":"1","language":[{"iso":"eng"}],"doi":"10.1016/j.cell.2017.11.001","publication_identifier":{"issn":["00928674"]},"month":"11","publisher":"Cell Press","department":[{"_id":"MiSi"}],"publication_status":"published","year":"2017","volume":171,"date_created":"2018-12-11T11:47:15Z","date_updated":"2021-01-12T08:03:15Z","author":[{"orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","last_name":"Gärtner","first_name":"Florian R","full_name":"Gärtner, Florian R"},{"full_name":"Ahmad, Zerkah","first_name":"Zerkah","last_name":"Ahmad"},{"full_name":"Rosenberger, Gerhild","first_name":"Gerhild","last_name":"Rosenberger"},{"full_name":"Fan, Shuxia","last_name":"Fan","first_name":"Shuxia"},{"full_name":"Nicolai, Leo","first_name":"Leo","last_name":"Nicolai"},{"full_name":"Busch, Benjamin","last_name":"Busch","first_name":"Benjamin"},{"full_name":"Yavuz, Gökce","last_name":"Yavuz","first_name":"Gökce"},{"full_name":"Luckner, Manja","last_name":"Luckner","first_name":"Manja"},{"full_name":"Ishikawa Ankerhold, Hellen","first_name":"Hellen","last_name":"Ishikawa Ankerhold"},{"full_name":"Hennel, Roman","first_name":"Roman","last_name":"Hennel"},{"first_name":"Alexandre","last_name":"Benechet","full_name":"Benechet, Alexandre"},{"full_name":"Lorenz, Michael","last_name":"Lorenz","first_name":"Michael"},{"last_name":"Chandraratne","first_name":"Sue","full_name":"Chandraratne, Sue"},{"full_name":"Schubert, Irene","last_name":"Schubert","first_name":"Irene"},{"full_name":"Helmer, Sebastian","first_name":"Sebastian","last_name":"Helmer"},{"full_name":"Striednig, Bianca","last_name":"Striednig","first_name":"Bianca"},{"last_name":"Stark","first_name":"Konstantin","full_name":"Stark, Konstantin"},{"full_name":"Janko, Marek","last_name":"Janko","first_name":"Marek"},{"full_name":"Böttcher, Ralph","first_name":"Ralph","last_name":"Böttcher"},{"full_name":"Verschoor, Admar","first_name":"Admar","last_name":"Verschoor"},{"full_name":"Leon, Catherine","last_name":"Leon","first_name":"Catherine"},{"last_name":"Gachet","first_name":"Christian","full_name":"Gachet, Christian"},{"full_name":"Gudermann, Thomas","last_name":"Gudermann","first_name":"Thomas"},{"last_name":"Mederos Y Schnitzler","first_name":"Michael","full_name":"Mederos Y Schnitzler, Michael"},{"last_name":"Pincus","first_name":"Zachary","full_name":"Pincus, Zachary"},{"first_name":"Matteo","last_name":"Iannacone","full_name":"Iannacone, Matteo"},{"first_name":"Rainer","last_name":"Haas","full_name":"Haas, Rainer"},{"full_name":"Wanner, Gerhard","first_name":"Gerhard","last_name":"Wanner"},{"first_name":"Kirsten","last_name":"Lauber","full_name":"Lauber, Kirsten"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"},{"last_name":"Massberg","first_name":"Steffen","full_name":"Massberg, Steffen"}],"publist_id":"7243","ec_funded":1},{"file_date_updated":"2020-07-14T12:47:34Z","publist_id":"7075","article_number":"14832","author":[{"first_name":"Frieda","last_name":"Kage","full_name":"Kage, Frieda"},{"full_name":"Winterhoff, Moritz","last_name":"Winterhoff","first_name":"Moritz"},{"last_name":"Dimchev","first_name":"Vanessa","full_name":"Dimchev, Vanessa"},{"last_name":"Müller","first_name":"Jan","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D","full_name":"Müller, Jan"},{"last_name":"Thalheim","first_name":"Tobias","full_name":"Thalheim, Tobias"},{"last_name":"Freise","first_name":"Anika","full_name":"Freise, Anika"},{"full_name":"Brühmann, Stefan","first_name":"Stefan","last_name":"Brühmann"},{"last_name":"Kollasser","first_name":"Jana","full_name":"Kollasser, Jana"},{"full_name":"Block, Jennifer","first_name":"Jennifer","last_name":"Block"},{"first_name":"Georgi A","last_name":"Dimchev","full_name":"Dimchev, Georgi A"},{"full_name":"Geyer, Matthias","last_name":"Geyer","first_name":"Matthias"},{"full_name":"Schnittler, Hams","last_name":"Schnittler","first_name":"Hams"},{"first_name":"Cord","last_name":"Brakebusch","full_name":"Brakebusch, Cord"},{"full_name":"Stradal, Theresia","first_name":"Theresia","last_name":"Stradal"},{"first_name":"Marie","last_name":"Carlier","full_name":"Carlier, Marie"},{"full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Käs, Josef","last_name":"Käs","first_name":"Josef"},{"full_name":"Faix, Jan","first_name":"Jan","last_name":"Faix"},{"full_name":"Rottner, Klemens","last_name":"Rottner","first_name":"Klemens"}],"date_updated":"2021-01-12T08:08:06Z","date_created":"2018-12-11T11:47:46Z","volume":8,"year":"2017","publication_status":"published","department":[{"_id":"MiSi"}],"publisher":"Nature Publishing Group","month":"03","publication_identifier":{"issn":["20411723"]},"doi":"10.1038/ncomms14832","language":[{"iso":"eng"}],"oa":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"},"quality_controlled":"1","abstract":[{"text":"Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.","lang":"eng"}],"type":"journal_article","pubrep_id":"902","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":9523746,"creator":"system","access_level":"open_access","file_name":"IST-2017-902-v1+1_Kage_et_al-2017-Nature_Communications.pdf","checksum":"dae30190291c3630e8102d8714a8d23e","date_updated":"2020-07-14T12:47:34Z","date_created":"2018-12-12T10:14:21Z","relation":"main_file","file_id":"5072"}],"_id":"659","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","status":"public","ddc":["570"],"title":"FMNL formins boost lamellipodial force generation","intvolume":" 8","day":"22","article_processing_charge":"No","has_accepted_license":"1","scopus_import":1,"date_published":"2017-03-22T00:00:00Z","publication":"Nature Communications","citation":{"mla":"Kage, Frieda, et al. “FMNL Formins Boost Lamellipodial Force Generation.” Nature Communications, vol. 8, 14832, Nature Publishing Group, 2017, doi:10.1038/ncomms14832.","short":"F. Kage, M. Winterhoff, V. Dimchev, J. Müller, T. Thalheim, A. Freise, S. Brühmann, J. Kollasser, J. Block, G.A. Dimchev, M. Geyer, H. Schnittler, C. Brakebusch, T. Stradal, M. Carlier, M.K. Sixt, J. Käs, J. Faix, K. Rottner, Nature Communications 8 (2017).","chicago":"Kage, Frieda, Moritz Winterhoff, Vanessa Dimchev, Jan Müller, Tobias Thalheim, Anika Freise, Stefan Brühmann, et al. “FMNL Formins Boost Lamellipodial Force Generation.” Nature Communications. Nature Publishing Group, 2017. https://doi.org/10.1038/ncomms14832.","ama":"Kage F, Winterhoff M, Dimchev V, et al. FMNL formins boost lamellipodial force generation. Nature Communications. 2017;8. doi:10.1038/ncomms14832","ista":"Kage F, Winterhoff M, Dimchev V, Müller J, Thalheim T, Freise A, Brühmann S, Kollasser J, Block J, Dimchev GA, Geyer M, Schnittler H, Brakebusch C, Stradal T, Carlier M, Sixt MK, Käs J, Faix J, Rottner K. 2017. FMNL formins boost lamellipodial force generation. Nature Communications. 8, 14832.","apa":"Kage, F., Winterhoff, M., Dimchev, V., Müller, J., Thalheim, T., Freise, A., … Rottner, K. (2017). FMNL formins boost lamellipodial force generation. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms14832","ieee":"F. Kage et al., “FMNL formins boost lamellipodial force generation,” Nature Communications, vol. 8. Nature Publishing Group, 2017."}},{"date_published":"2017-04-28T00:00:00Z","publication":"Journal of Biological Chemistry","citation":{"ama":"Horsthemke M, Bachg A, Groll K, et al. Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. Journal of Biological Chemistry. 2017;292(17):7258-7273. doi:10.1074/jbc.M116.766923","ista":"Horsthemke M, Bachg A, Groll K, Moyzio S, Müther B, Hemkemeyer S, Wedlich Söldner R, Sixt MK, Tacke S, Bähler M, Hanley P. 2017. Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. Journal of Biological Chemistry. 292(17), 7258–7273.","apa":"Horsthemke, M., Bachg, A., Groll, K., Moyzio, S., Müther, B., Hemkemeyer, S., … Hanley, P. (2017). Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology. https://doi.org/10.1074/jbc.M116.766923","ieee":"M. Horsthemke et al., “Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion,” Journal of Biological Chemistry, vol. 292, no. 17. American Society for Biochemistry and Molecular Biology, pp. 7258–7273, 2017.","mla":"Horsthemke, Markus, et al. “Multiple Roles of Filopodial Dynamics in Particle Capture and Phagocytosis and Phenotypes of Cdc42 and Myo10 Deletion.” Journal of Biological Chemistry, vol. 292, no. 17, American Society for Biochemistry and Molecular Biology, 2017, pp. 7258–73, doi:10.1074/jbc.M116.766923.","short":"M. Horsthemke, A. Bachg, K. Groll, S. Moyzio, B. Müther, S. Hemkemeyer, R. Wedlich Söldner, M.K. Sixt, S. Tacke, M. Bähler, P. Hanley, Journal of Biological Chemistry 292 (2017) 7258–7273.","chicago":"Horsthemke, Markus, Anne Bachg, Katharina Groll, Sven Moyzio, Barbara Müther, Sandra Hemkemeyer, Roland Wedlich Söldner, et al. “Multiple Roles of Filopodial Dynamics in Particle Capture and Phagocytosis and Phenotypes of Cdc42 and Myo10 Deletion.” Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology, 2017. https://doi.org/10.1074/jbc.M116.766923."},"article_type":"original","page":"7258 - 7273","day":"28","has_accepted_license":"1","scopus_import":1,"file":[{"file_name":"2017_JBC_Horsthemke.pdf","access_level":"open_access","file_size":5647880,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"6971","date_created":"2019-10-24T15:25:42Z","date_updated":"2020-07-14T12:47:37Z","checksum":"d488162874326a4bb056065fa549dc4a"}],"oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"668","title":"Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion","ddc":["570"],"status":"public","intvolume":" 292","abstract":[{"lang":"eng","text":"Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading."}],"issue":"17","type":"journal_article","doi":"10.1074/jbc.M116.766923","language":[{"iso":"eng"}],"oa":1,"quality_controlled":"1","month":"04","publication_identifier":{"issn":["00219258"]},"author":[{"full_name":"Horsthemke, Markus","first_name":"Markus","last_name":"Horsthemke"},{"full_name":"Bachg, Anne","first_name":"Anne","last_name":"Bachg"},{"full_name":"Groll, Katharina","last_name":"Groll","first_name":"Katharina"},{"full_name":"Moyzio, Sven","first_name":"Sven","last_name":"Moyzio"},{"full_name":"Müther, Barbara","last_name":"Müther","first_name":"Barbara"},{"last_name":"Hemkemeyer","first_name":"Sandra","full_name":"Hemkemeyer, Sandra"},{"first_name":"Roland","last_name":"Wedlich Söldner","full_name":"Wedlich Söldner, Roland"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt"},{"full_name":"Tacke, Sebastian","last_name":"Tacke","first_name":"Sebastian"},{"first_name":"Martin","last_name":"Bähler","full_name":"Bähler, Martin"},{"last_name":"Hanley","first_name":"Peter","full_name":"Hanley, Peter"}],"date_updated":"2021-01-12T08:08:34Z","date_created":"2018-12-11T11:47:49Z","volume":292,"year":"2017","publication_status":"published","publisher":"American Society for Biochemistry and Molecular Biology","department":[{"_id":"MiSi"}],"file_date_updated":"2020-07-14T12:47:37Z","publist_id":"7059"}]