[{"citation":{"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>","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.","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.","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)."},"department":[{"_id":"MiSi"}],"month":"07","external_id":{"pmid":["42414599"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"07","article_type":"original","scopus_import":"1","status":"public","publisher":"Springer Nature","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"year":"2026","OA_type":"gold","oa_version":"Published Version","quality_controlled":"1","author":[{"first_name":"Philippe G","last_name":"Dehio","id":"b769738e-a003-11ee-b1b8-9030316e0d59","full_name":"Dehio, Philippe G"},{"full_name":"Michard, Céline","last_name":"Michard","first_name":"Céline"},{"full_name":"Yam-Puc, Juan Carlos","first_name":"Juan Carlos","last_name":"Yam-Puc"},{"last_name":"Martí I Líndez","first_name":"Adrià Arnau","full_name":"Martí I Líndez, Adrià Arnau"},{"full_name":"Jandke, Anett","first_name":"Anett","last_name":"Jandke"},{"full_name":"Unterstab, Gunhild","first_name":"Gunhild","last_name":"Unterstab"},{"last_name":"Fabre","first_name":"Lucien","full_name":"Fabre, Lucien"},{"full_name":"Sauteur, Loïc","last_name":"Sauteur","first_name":"Loïc"},{"full_name":"Artinger, Marc","first_name":"Marc","last_name":"Artinger"},{"last_name":"Legler","first_name":"Daniel F.","full_name":"Legler, Daniel F."},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"},{"full_name":"Schaefer, Thorsten","last_name":"Schaefer","first_name":"Thorsten"},{"last_name":"Wymann","first_name":"Matthias P.","full_name":"Wymann, Matthias P."},{"first_name":"Klaus","last_name":"Okkenhaug","full_name":"Okkenhaug, Klaus"},{"first_name":"Thierry","last_name":"Soldati","full_name":"Soldati, Thierry"},{"last_name":"Mehling","first_name":"Matthias","orcid":"0000-0001-8599-1226","full_name":"Mehling, Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Hess, Christoph","last_name":"Hess","first_name":"Christoph"}],"publication":"EMBO Reports","publication_status":"epub_ahead","DOAJ_listed":"1","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.","oa":1,"language":[{"iso":"eng"}],"OA_place":"publisher","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.","main_file_link":[{"url":"https://doi.org/10.1038/s44319-026-00861-x","open_access":"1"}],"pmid":1,"date_published":"2026-07-07T00:00:00Z","title":"A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration","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."}],"doi":"10.1038/s44319-026-00861-x","publication_identifier":{"eissn":["1469-3178"]},"date_updated":"2026-07-20T14:28:59Z","researchdata_availability":"yes","article_processing_charge":"Yes (via OA deal)","_id":"22371","das_tickbox":"1","date_created":"2026-07-19T22:01:48Z","supplementarymaterial":"yes","type":"journal_article"},{"page":"902 - 909","date_created":"2018-12-11T11:47:50Z","type":"journal_article","article_processing_charge":"Yes","_id":"672","ddc":["570"],"corr_author":"1","intvolume":"        19","pubrep_id":"900","issue":"5","publication_identifier":{"issn":["2211-1247"]},"doi":"10.1016/j.celrep.2017.04.027","date_updated":"2025-09-10T14:27:34Z","title":"Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia","date_published":"2017-05-02T00:00:00Z","abstract":[{"lang":"eng","text":"Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration."}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","oa":1,"publication_status":"published","publication":"Cell Reports","language":[{"iso":"eng"}],"isi":1,"project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556","call_identifier":"FP7"},{"call_identifier":"FWF","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"author":[{"id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari","first_name":"Kari","orcid":"0000-0001-7829-3518","last_name":"Vaahtomeri"},{"id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus","first_name":"Markus","last_name":"Brown"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid","first_name":"Ingrid","last_name":"De Vries"},{"last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Mehling, Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87","last_name":"Mehling","orcid":"0000-0001-8599-1226","first_name":"Matthias"},{"last_name":"Kaufmann","first_name":"Walter","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179"}],"quality_controlled":"1","year":"2017","oa_version":"Published Version","file_date_updated":"2020-07-14T12:47:38Z","publisher":"Cell Press","ec_funded":1,"file":[{"date_updated":"2020-07-14T12:47:38Z","date_created":"2018-12-12T10:14:54Z","content_type":"application/pdf","access_level":"open_access","file_size":2248814,"checksum":"8fdddaab1f1d76a6ec9ca94dcb6b07a2","file_id":"5109","file_name":"IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf","creator":"system","relation":"main_file"}],"status":"public","scopus_import":"1","tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"has_accepted_license":"1","day":"02","month":"05","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","volume":19,"external_id":{"isi":["000402124100002"]},"citation":{"ista":"Vaahtomeri K, Brown M, Hauschild R, de Vries I, Leithner AF, Mehling M, Kaufmann W, Sixt MK. 2017. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports. 19(5), 902–909.","chicago":"Vaahtomeri, Kari, Markus Brown, Robert Hauschild, Ingrid de Vries, Alexander F Leithner, Matthias Mehling, Walter Kaufmann, and Michael K Sixt. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>.","ama":"Vaahtomeri K, Brown M, Hauschild R, et al. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. <i>Cell Reports</i>. 2017;19(5):902-909. doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>","ieee":"K. Vaahtomeri <i>et al.</i>, “Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia,” <i>Cell Reports</i>, vol. 19, no. 5. Cell Press, pp. 902–909, 2017.","apa":"Vaahtomeri, K., Brown, M., Hauschild, R., de Vries, I., Leithner, A. F., Mehling, M., … Sixt, M. K. (2017). Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>","short":"K. Vaahtomeri, M. Brown, R. Hauschild, I. de Vries, A.F. Leithner, M. Mehling, W. Kaufmann, M.K. Sixt, Cell Reports 19 (2017) 902–909.","mla":"Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>, vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>."},"publist_id":"7052"},{"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","volume":6,"external_id":{"isi":["000387118300001"]},"month":"11","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"ToBo"}],"publist_id":"6204","citation":{"ista":"Schwarz J, Bierbaum V, Merrin J, Frank T, Hauschild R, Bollenbach MT, Tay S, Sixt MK, Mehling M. 2016. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. Scientific Reports. 6, 36440.","ama":"Schwarz J, Bierbaum V, Merrin J, et al. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. <i>Scientific Reports</i>. 2016;6. doi:<a href=\"https://doi.org/10.1038/srep36440\">10.1038/srep36440</a>","chicago":"Schwarz, Jan, Veronika Bierbaum, Jack Merrin, Tino Frank, Robert Hauschild, Mark Tobias Bollenbach, Savaş Tay, Michael K Sixt, and Matthias Mehling. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” <i>Scientific Reports</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/srep36440\">https://doi.org/10.1038/srep36440</a>.","ieee":"J. Schwarz <i>et al.</i>, “A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients,” <i>Scientific Reports</i>, vol. 6. Nature Publishing Group, 2016.","apa":"Schwarz, J., Bierbaum, V., Merrin, J., Frank, T., Hauschild, R., Bollenbach, M. T., … Mehling, M. (2016). A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. <i>Scientific Reports</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/srep36440\">https://doi.org/10.1038/srep36440</a>","short":"J. Schwarz, V. Bierbaum, J. Merrin, T. Frank, R. Hauschild, M.T. Bollenbach, S. Tay, M.K. Sixt, M. Mehling, Scientific Reports 6 (2016).","mla":"Schwarz, Jan, et al. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” <i>Scientific Reports</i>, vol. 6, 36440, Nature Publishing Group, 2016, doi:<a href=\"https://doi.org/10.1038/srep36440\">10.1038/srep36440</a>."},"has_accepted_license":"1","publisher":"Nature Publishing Group","scopus_import":"1","status":"public","file":[{"relation":"main_file","creator":"system","file_name":"IST-2017-744-v1+1_srep36440.pdf","file_id":"4756","access_level":"open_access","file_size":2353456,"content_type":"application/pdf","date_created":"2018-12-12T10:09:32Z","date_updated":"2018-12-12T10:09:32Z"}],"ec_funded":1,"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"day":"07","quality_controlled":"1","oa_version":"Published Version","article_number":"36440","file_date_updated":"2018-12-12T10:09:32Z","year":"2016","isi":1,"project":[{"call_identifier":"FP7","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A603A2-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"author":[{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","first_name":"Jan","last_name":"Schwarz"},{"last_name":"Bierbaum","first_name":"Veronika","full_name":"Bierbaum, Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Merrin","first_name":"Jack","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tino","last_name":"Frank","full_name":"Frank, Tino"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Mark Tobias","orcid":"0000-0003-4398-476X","first_name":"Mark Tobias","last_name":"Bollenbach"},{"full_name":"Tay, Savaş","last_name":"Tay","first_name":"Savaş"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","orcid":"0000-0002-6620-9179","first_name":"Michael K"},{"last_name":"Mehling","first_name":"Matthias","orcid":"0000-0001-8599-1226","full_name":"Mehling, Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87"}],"acknowledgement":"This work was supported by the Swiss National Science Foundation (Ambizione fellowship; PZ00P3-154733 to M.M.), the Swiss Multiple Sclerosis Society (research support to M.M.), a fellowship from the Boehringer Ingelheim Fonds (BIF) to J.S., the European Research Council (grant ERC GA 281556) and a START award from the Austrian Science Foundation (FWF) to M.S. #BioimagingFacility","language":[{"iso":"eng"}],"oa":1,"publication_status":"published","publication":"Scientific Reports","date_updated":"2025-09-22T09:56:13Z","doi":"10.1038/srep36440","abstract":[{"lang":"eng","text":"Cellular locomotion is a central hallmark of eukaryotic life. It is governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present as a spatial or temporal gradient. Here, we developed a microfluidic chamber that allows measurement of cell migration in combined response to surface immobilized and soluble molecular gradients. As a proof of principle we study the response of dendritic cells to their major guidance cues, chemokines. The majority of data on chemokine gradient sensing is based on in vitro studies employing soluble gradients. Despite evidence suggesting that in vivo chemokines are often immobilized to sugar residues, limited information is available how cells respond to immobilized chemokines. We tracked migration of dendritic cells towards immobilized gradients of the chemokine CCL21 and varying superimposed soluble gradients of CCL19. Differential migratory patterns illustrate the potential of our setup to quantitatively study the competitive response to both types of gradients. Beyond chemokines our approach is broadly applicable to alternative systems of chemo- and haptotaxis such as cells migrating along gradients of adhesion receptor ligands vs. any soluble cue. \r\n"}],"title":"A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients","date_published":"2016-11-07T00:00:00Z","intvolume":"         6","pubrep_id":"744","type":"journal_article","date_created":"2018-12-11T11:50:27Z","ddc":["579"],"_id":"1154","article_processing_charge":"No"}]