---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '22371'
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.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
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)
article_type: original
author:
- first_name: Philippe G
  full_name: Dehio, Philippe G
  id: b769738e-a003-11ee-b1b8-9030316e0d59
  last_name: Dehio
- first_name: Céline
  full_name: Michard, Céline
  last_name: Michard
- first_name: Juan Carlos
  full_name: Yam-Puc, Juan Carlos
  last_name: Yam-Puc
- first_name: Adrià Arnau
  full_name: Martí I Líndez, Adrià Arnau
  last_name: Martí I Líndez
- first_name: Anett
  full_name: Jandke, Anett
  last_name: Jandke
- first_name: Gunhild
  full_name: Unterstab, Gunhild
  last_name: Unterstab
- first_name: Lucien
  full_name: Fabre, Lucien
  last_name: Fabre
- first_name: Loïc
  full_name: Sauteur, Loïc
  last_name: Sauteur
- first_name: Marc
  full_name: Artinger, Marc
  last_name: Artinger
- first_name: Daniel F.
  full_name: Legler, Daniel F.
  last_name: Legler
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Thorsten
  full_name: Schaefer, Thorsten
  last_name: Schaefer
- first_name: Matthias P.
  full_name: Wymann, Matthias P.
  last_name: Wymann
- first_name: Klaus
  full_name: Okkenhaug, Klaus
  last_name: Okkenhaug
- first_name: Thierry
  full_name: Soldati, Thierry
  last_name: Soldati
- first_name: Matthias
  full_name: Mehling, Matthias
  id: 3C23B994-F248-11E8-B48F-1D18A9856A87
  last_name: Mehling
  orcid: 0000-0001-8599-1226
- first_name: Christoph
  full_name: Hess, Christoph
  last_name: Hess
citation:
  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>
  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>
  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>.
  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.
  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).
das_tickbox: '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."
date_created: 2026-07-19T22:01:48Z
date_published: 2026-07-07T00:00:00Z
date_updated: 2026-07-20T14:28:59Z
day: '07'
department:
- _id: MiSi
doi: 10.1038/s44319-026-00861-x
external_id:
  pmid:
  - '42414599'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s44319-026-00861-x
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: EMBO Reports
publication_identifier:
  eissn:
  - 1469-3178
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid
  cell migration
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...