{"title":"Adaptive pathfinding by nucleokinesis during amoeboid migration","quality_controlled":"1","status":"public","publisher":"Embo Press","scopus_import":"1","oa":1,"oa_version":"Published Version","date_created":"2023-08-01T08:59:06Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"NanoFab"},{"_id":"Bio"}],"abstract":[{"text":"Motile cells moving in multicellular organisms encounter microenvironments of locally heterogeneous mechanochemical composition. Individual compositional parameters like chemotactic signals, adhesiveness, and pore sizes are well known to be sensed by motile cells, providing individual guidance cues for cellular pathfinding. However, motile cells encounter diverse mechanochemical signals at the same time, raising the question of how cells respond to locally diverse and potentially competing signals on their migration routes. Here, we reveal that motile amoeboid cells require nuclear repositioning, termed nucleokinesis, for adaptive pathfinding in heterogeneous mechanochemical microenvironments. Using mammalian immune cells and the amoeba<jats:italic>Dictyostelium discoideum</jats:italic>, we discover that frequent, rapid and long-distance nucleokinesis is a basic component of amoeboid pathfinding, enabling cells to reorientate quickly between locally competing cues. Amoeboid nucleokinesis comprises a two-step cell polarity switch and is driven by myosin II-forces, sliding the nucleus from a ‘losing’ to the ‘winning’ leading edge to re-adjust the nuclear to the cellular path. Impaired nucleokinesis distorts fast path adaptions and causes cellular arrest in the microenvironment. Our findings establish that nucleokinesis is required for amoeboid cell navigation. Given that motile single-cell amoebae, many immune cells, and some cancer cells utilize an amoeboid migration strategy, these results suggest that amoeboid nucleokinesis underlies cellular navigation during unicellular biology, immunity, and disease.","lang":"eng"}],"date_published":"2023-11-21T00:00:00Z","publication_status":"published","article_processing_charge":"Yes (via OA deal)","month":"11","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"date_updated":"2023-11-27T08:47:45Z","pmid":1,"file":[{"date_updated":"2023-11-27T08:45:56Z","date_created":"2023-11-27T08:45:56Z","file_size":4862497,"file_id":"14611","success":1,"relation":"main_file","checksum":"6261d0041c7e8d284c39712c40079730","file_name":"2023_EmboJournal_Kroll.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf"}],"type":"journal_article","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","day":"21","ddc":["570"],"file_date_updated":"2023-11-27T08:45:56Z","acknowledgement":"We thank Christoph Mayr and Bingzhi Wang for initial experiments on amoeboid nucleokinesis, Ana-Maria Lennon-Duménil and Aline Yatim for bone marrow from MyoIIA-Flox*CD11c-Cre mice, Michael Sixt and Aglaja Kopf for EMTB-mCherry, EB3-mCherry, Lifeact-GFP, Lfc knockout, and Myh9-GFP expressing HoxB8 cells, Malte Benjamin Braun, Mauricio Ruiz, and Madeleine T. Schmitt for critical reading of the manuscript, and the Core Facility Bioimaging, the Core Facility Flow Cytometry, and the Animal Core Facility of the Biomedical Center (BMC) for excellent support. This study was supported by the Peter Hans Hofschneider Professorship of the foundation “Stiftung Experimentelle Biomedizin” (to JR), the LMU Institutional Strategy LMU-Excellent within the framework of the German Excellence Initiative (to JR), and the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; SFB914 project A12, to JR), and the CZI grant DAF2020-225401 (https://doi.org/10.37921/120055ratwvi) from the Chan Zuckerberg Initiative DAF (to RH; an advised fund of Silicon Valley Community Foundation (funder https://doi.org/10.13039/100014989)). Open Access funding enabled and organized by Projekt DEAL.","year":"2023","language":[{"iso":"eng"}],"article_number":"e114557","_id":"13342","article_type":"original","citation":{"ista":"Kroll J, Hauschild R, Kuznetcov A, Stefanowski K, Hermann MD, Merrin J, Shafeek LB, Müller-Taubenberger A, Renkawitz J. 2023. Adaptive pathfinding by nucleokinesis during amoeboid migration. EMBO Journal., e114557.","chicago":"Kroll, Janina, Robert Hauschild, Arthur Kuznetcov, Kasia Stefanowski, Monika D. Hermann, Jack Merrin, Lubuna B Shafeek, Annette Müller-Taubenberger, and Jörg Renkawitz. “Adaptive Pathfinding by Nucleokinesis during Amoeboid Migration.” <i>EMBO Journal</i>. Embo Press, 2023. <a href=\"https://doi.org/10.15252/embj.2023114557\">https://doi.org/10.15252/embj.2023114557</a>.","apa":"Kroll, J., Hauschild, R., Kuznetcov, A., Stefanowski, K., Hermann, M. D., Merrin, J., … Renkawitz, J. (2023). Adaptive pathfinding by nucleokinesis during amoeboid migration. <i>EMBO Journal</i>. Embo Press. <a href=\"https://doi.org/10.15252/embj.2023114557\">https://doi.org/10.15252/embj.2023114557</a>","ama":"Kroll J, Hauschild R, Kuznetcov A, et al. Adaptive pathfinding by nucleokinesis during amoeboid migration. <i>EMBO Journal</i>. 2023. doi:<a href=\"https://doi.org/10.15252/embj.2023114557\">10.15252/embj.2023114557</a>","short":"J. Kroll, R. Hauschild, A. Kuznetcov, K. Stefanowski, M.D. Hermann, J. Merrin, L.B. Shafeek, A. Müller-Taubenberger, J. Renkawitz, EMBO Journal (2023).","mla":"Kroll, Janina, et al. “Adaptive Pathfinding by Nucleokinesis during Amoeboid Migration.” <i>EMBO Journal</i>, e114557, Embo Press, 2023, doi:<a href=\"https://doi.org/10.15252/embj.2023114557\">10.15252/embj.2023114557</a>.","ieee":"J. Kroll <i>et al.</i>, “Adaptive pathfinding by nucleokinesis during amoeboid migration,” <i>EMBO Journal</i>. Embo Press, 2023."},"external_id":{"pmid":["37987147"]},"publication_identifier":{"issn":["0261-4189"],"eissn":["1460-2075"]},"doi":"10.15252/embj.2023114557","has_accepted_license":"1","publication":"EMBO Journal","author":[{"first_name":"Janina","last_name":"Kroll","full_name":"Kroll, Janina"},{"orcid":"0000-0001-9843-3522","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kuznetcov, Arthur","last_name":"Kuznetcov","first_name":"Arthur"},{"full_name":"Stefanowski, Kasia","last_name":"Stefanowski","first_name":"Kasia"},{"last_name":"Hermann","first_name":"Monika D.","full_name":"Hermann, Monika D."},{"orcid":"0000-0001-5145-4609","last_name":"Merrin","first_name":"Jack","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-7180-6050","last_name":"Shafeek","first_name":"Lubuna B","full_name":"Shafeek, Lubuna B","id":"3CD37A82-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Müller-Taubenberger, Annette","first_name":"Annette","last_name":"Müller-Taubenberger"},{"orcid":"0000-0003-2856-3369","last_name":"Renkawitz","first_name":"Jörg","full_name":"Renkawitz, Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"}]}