---
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'
...
---
_id: '672'
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.
article_processing_charge: Yes
author:
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
- first_name: Markus
  full_name: Brown, Markus
  id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
  last_name: Brown
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Ingrid
  full_name: De Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: De Vries
- first_name: Alexander F
  full_name: Leithner, Alexander F
  id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
  last_name: Leithner
  orcid: 0000-0002-1073-744X
- first_name: Matthias
  full_name: Mehling, Matthias
  id: 3C23B994-F248-11E8-B48F-1D18A9856A87
  last_name: Mehling
  orcid: 0000-0001-8599-1226
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  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>
  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>
  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>.
  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.
  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.
  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>.
  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.
corr_author: '1'
date_created: 2018-12-11T11:47:50Z
date_published: 2017-05-02T00:00:00Z
date_updated: 2025-09-10T14:27:34Z
day: '02'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
- _id: EM-Fac
doi: 10.1016/j.celrep.2017.04.027
ec_funded: 1
external_id:
  isi:
  - '000402124100002'
file:
- access_level: open_access
  checksum: 8fdddaab1f1d76a6ec9ca94dcb6b07a2
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:14:54Z
  date_updated: 2020-07-14T12:47:38Z
  file_id: '5109'
  file_name: IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf
  file_size: 2248814
  relation: main_file
file_date_updated: 2020-07-14T12:47:38Z
has_accepted_license: '1'
intvolume: '        19'
isi: 1
issue: '5'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '05'
oa: 1
oa_version: Published Version
page: 902 - 909
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '281556'
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
publication: Cell Reports
publication_identifier:
  issn:
  - 2211-1247
publication_status: published
publisher: Cell Press
publist_id: '7052'
pubrep_id: '900'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration
  across lymphatic endothelia
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)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 19
year: '2017'
...
---
_id: '1154'
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"
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'
article_number: '36440'
article_processing_charge: No
author:
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Veronika
  full_name: Bierbaum, Veronika
  id: 3FD04378-F248-11E8-B48F-1D18A9856A87
  last_name: Bierbaum
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Tino
  full_name: Frank, Tino
  last_name: Frank
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
- first_name: Savaş
  full_name: Tay, Savaş
  last_name: Tay
- 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: Matthias
  full_name: Mehling, Matthias
  id: 3C23B994-F248-11E8-B48F-1D18A9856A87
  last_name: Mehling
  orcid: 0000-0001-8599-1226
citation:
  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>
  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>
  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.
  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.
  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>.
  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).
date_created: 2018-12-11T11:50:27Z
date_published: 2016-11-07T00:00:00Z
date_updated: 2025-09-22T09:56:13Z
day: '07'
ddc:
- '579'
department:
- _id: MiSi
- _id: NanoFab
- _id: Bio
- _id: ToBo
doi: 10.1038/srep36440
ec_funded: 1
external_id:
  isi:
  - '000387118300001'
file:
- access_level: open_access
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:09:32Z
  date_updated: 2018-12-12T10:09:32Z
  file_id: '4756'
  file_name: IST-2017-744-v1+1_srep36440.pdf
  file_size: 2353456
  relation: main_file
file_date_updated: 2018-12-12T10:09:32Z
has_accepted_license: '1'
intvolume: '         6'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '281556'
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
publication: Scientific Reports
publication_status: published
publisher: Nature Publishing Group
publist_id: '6204'
pubrep_id: '744'
quality_controlled: '1'
scopus_import: '1'
status: public
title: A microfluidic device for measuring cell migration towards substrate bound
  and soluble chemokine gradients
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 6
year: '2016'
...