{"oa":1,"publisher":"Springer Nature","department":[{"_id":"MiSi"}],"publication":"EMBO Reports","status":"public","OA_place":"publisher","external_id":{"pmid":["42414599"]},"quality_controlled":"1","das_tickbox":"1","acknowledgement":"We thank the microscopy core facility of the Department of Biomedicine at the University and University Hospital of Basel for their technical support. This research was technically supported by the Scientific Service Units (SSU) of ISTA through resources provided by the Imaging & Optics Facility (IOF) and the Lab Support Facility (LSF). CH was supported by the Swiss National Science Foundation (SNSF) (310030B_201277; 310030_192677; FZEB-0-180487), the ZBF Program Award 2025 (Hans Zäslin Bustany Foundation), and the Novartis Foundation for Medical-Biological Research (NFMBR) (#23A070). PD was supported by the Swiss Academy for Medical Sciences (SAMW) and SNSF (183980, 225441), the NFMBR (#23A070), AlumniMedizin Basel, and the Freiwillige Akademische Gesellschaft Basel. DFL was supported by the SNSF (220205). Open access funding provided by University of Basel.","article_processing_charge":"Yes (via OA deal)","_id":"22371","OA_type":"gold","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","main_file_link":[{"url":"https://doi.org/10.1038/s44319-026-00861-x","open_access":"1"}],"pmid":1,"date_created":"2026-07-19T22:01:48Z","day":"07","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"DOAJ_listed":"1","publication_status":"epub_ahead","date_published":"2026-07-07T00:00:00Z","language":[{"iso":"eng"}],"researchdata_availability":"yes","article_type":"original","scopus_import":"1","month":"07","doi":"10.1038/s44319-026-00861-x","oa_version":"Published Version","author":[{"id":"b769738e-a003-11ee-b1b8-9030316e0d59","full_name":"Dehio, Philippe G","last_name":"Dehio","first_name":"Philippe G"},{"last_name":"Michard","first_name":"Céline","full_name":"Michard, Céline"},{"full_name":"Yam-Puc, Juan Carlos","last_name":"Yam-Puc","first_name":"Juan Carlos"},{"full_name":"Martí I Líndez, Adrià Arnau","last_name":"Martí I Líndez","first_name":"Adrià Arnau"},{"first_name":"Anett","last_name":"Jandke","full_name":"Jandke, Anett"},{"first_name":"Gunhild","last_name":"Unterstab","full_name":"Unterstab, Gunhild"},{"first_name":"Lucien","last_name":"Fabre","full_name":"Fabre, Lucien"},{"last_name":"Sauteur","first_name":"Loïc","full_name":"Sauteur, Loïc"},{"full_name":"Artinger, Marc","first_name":"Marc","last_name":"Artinger"},{"full_name":"Legler, Daniel F.","last_name":"Legler","first_name":"Daniel F."},{"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":"Schaefer, Thorsten","first_name":"Thorsten","last_name":"Schaefer"},{"full_name":"Wymann, Matthias P.","first_name":"Matthias P.","last_name":"Wymann"},{"full_name":"Okkenhaug, Klaus","first_name":"Klaus","last_name":"Okkenhaug"},{"full_name":"Soldati, Thierry","first_name":"Thierry","last_name":"Soldati"},{"first_name":"Matthias","orcid":"0000-0001-8599-1226","last_name":"Mehling","full_name":"Mehling, Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Hess, Christoph","last_name":"Hess","first_name":"Christoph"}],"supplementarymaterial":"yes","abstract":[{"lang":"eng","text":"Amoeboid cell migration is key to efficient T cell immunity. Spatial polarization of organelles within cells, including endo-lysosomes, is a prerequisite of migration. However, how ultrastructural polarization is linked to the signaling requirements governing T cell migration remains unknown. Here we show that signaling molecules generated by endo-lysosome-localized kinases regulate velocity of amoeboid migration. Specifically, imaging of T cells identifies accumulation of endo-lysosomes decorated with the lipid kinases VPS34–PIKfyve at the uropod of polarized cells. Activity of VPS34 and PIKfyve regulates speed, but not directedness, of migrating T cells. Mechanistically, PI(3,5)P2 generated by the sequential action of VPS34 and PIKfyve, mediates Ca2+ efflux from lysosomes via the mucolipin TRP cation channel 1 (TRPML1), thus controlling activity of myosin IIA and hence the generation of propulsive force through retrograde actin flow. The VPS34–PIKfyve kinases also regulate velocity of myeloid cells, as well as of the amoeba Dictyostelium discoideum – establishing the axis as an evolutionarily conserved speed control system of amoeboid cell migration."}],"citation":{"chicago":"Dehio, Philippe G, Céline Michard, Juan Carlos Yam-Puc, Adrià Arnau Martí I Líndez, Anett Jandke, Gunhild Unterstab, Lucien Fabre, et al. “A Conserved VPS34-PIKfyve-TRPML1-Myosin II Axis Regulates the Speed of Amoeboid Cell Migration.” <i>EMBO Reports</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s44319-026-00861-x\">https://doi.org/10.1038/s44319-026-00861-x</a>.","ista":"Dehio PG, Michard C, Yam-Puc JC, Martí I Líndez AA, Jandke A, Unterstab G, Fabre L, Sauteur L, Artinger M, Legler DF, Sixt MK, Schaefer T, Wymann MP, Okkenhaug K, Soldati T, Mehling M, Hess C. 2026. A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration. EMBO Reports.","ieee":"P. G. Dehio <i>et al.</i>, “A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration,” <i>EMBO Reports</i>. Springer Nature, 2026.","mla":"Dehio, Philippe G., et al. “A Conserved VPS34-PIKfyve-TRPML1-Myosin II Axis Regulates the Speed of Amoeboid Cell Migration.” <i>EMBO Reports</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s44319-026-00861-x\">10.1038/s44319-026-00861-x</a>.","short":"P.G. Dehio, C. Michard, J.C. Yam-Puc, A.A. Martí I Líndez, A. Jandke, G. Unterstab, L. Fabre, L. Sauteur, M. Artinger, D.F. Legler, M.K. Sixt, T. Schaefer, M.P. Wymann, K. Okkenhaug, T. Soldati, M. Mehling, C. Hess, EMBO Reports (2026).","apa":"Dehio, P. G., Michard, C., Yam-Puc, J. C., Martí I Líndez, A. A., Jandke, A., Unterstab, G., … Hess, C. (2026). A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration. <i>EMBO Reports</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s44319-026-00861-x\">https://doi.org/10.1038/s44319-026-00861-x</a>","ama":"Dehio PG, Michard C, Yam-Puc JC, et al. A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration. <i>EMBO Reports</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s44319-026-00861-x\">10.1038/s44319-026-00861-x</a>"},"date_updated":"2026-07-20T14:28:59Z","publication_identifier":{"eissn":["1469-3178"]},"type":"journal_article","title":"A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration","dataavailabilitystatement":"The analysis workflow to quantify vesicle localization can be accessed on GitHub (https://github.com/loicsauteur/vesicle-analysis, version 0.1.1).\r\n\r\nThe source data of this paper are collected in the following database record: biostudies:S-SCDT-10_1038-S44319-026-00861-x.","year":"2026"}