---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20082'
abstract:
- lang: eng
  text: Efficient immune responses rely on the capacity of leukocytes to traverse
    diverse and complex tissues. To meet such changing environmental conditions, leukocytes
    usually adopt an ameboid configuration, using their forward-positioned nucleus
    as a probe to identify and follow the path of least resistance among pre-existing
    pores. We show that, in dense environments where even the largest pores preclude
    free passage, leukocytes position their nucleus behind the centrosome and organelles.
    The local compression imposed on the cell body by its surroundings triggers assembly
    of a central F-actin pool, located between cell front and nucleus. Central actin
    pushes outward to transiently dilate a path for organelles and nucleus. Pools
    of central and front actin are tightly coupled and experimental depletion of the
    central pool enhances actin accumulation and protrusion formation at the cell
    front. Although this shifted balance speeds up cells in permissive environments,
    migration in restrictive environments is impaired, as the unleashed leading edge
    dissociates from the trapped cell body. Our findings establish an actin regulatory
    loop that balances path dilation with advancement of the leading edge to maintain
    cellular coherence.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: This research was supported by the Scientific Service Units of ISTA
  through resources provided by the Imaging and Optics, Preclinical and Lab Support
  Facilities. In particular, we thank M. A. Symth and F. G. G. Leite, from the Virus
  Service Team, who helped generating the lentiviral particles used in this study.
  We thank all the members of the Sixt group for valuable discussions and feedback,
  in particular, I. Mayer, for helping with T cell isolation and Z. (P.) Li for providing
  the Actin–GFP DC line. We are also thankful to J. Mandl and C. Shen for their feedback
  during the writing of this manuscript. This work was supported by a European Research
  Council grant ERC-SyG 101071793 to M.S. M.J.A. was supported by an HFSP Postdoctoral
  Fellowship LTF 177 2021 and A.J.G. by a Lise Meitner Fellowship of the FWF (Austrian
  Science Fund). Y.F. was supported by the AMED-CREST (JP19gm1310005), the Medical
  Research Center Initiative for High Depth Omics and CURE:JPMXP1323015486 for MIB,
  Kyushu University. Open access funding provided by Institute of Science and Technology
  (IST Austria).
article_processing_charge: Yes (via OA deal)
article_type: letter_note
author:
- first_name: Patricia
  full_name: Dos Reis Rodrigues, Patricia
  id: 26E95904-5160-11E9-9C0B-C5B0DC97E90F
  last_name: Dos Reis Rodrigues
  orcid: 0000-0003-1681-508X
- first_name: Mario
  full_name: Avellaneda Sarrió, Mario
  id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E
  last_name: Avellaneda Sarrió
  orcid: 0000-0001-6406-524X
- first_name: Nikola
  full_name: Canigova, Nikola
  id: 3795523E-F248-11E8-B48F-1D18A9856A87
  last_name: Canigova
  orcid: 0000-0002-8518-5926
- first_name: Florian R
  full_name: Gärtner, Florian R
  id: 397A88EE-F248-11E8-B48F-1D18A9856A87
  last_name: Gärtner
  orcid: 0000-0001-6120-3723
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
- first_name: Michael
  full_name: Riedl, Michael
  id: 3BE60946-F248-11E8-B48F-1D18A9856A87
  last_name: Riedl
  orcid: 0000-0003-4844-6311
- first_name: Ingrid
  full_name: De Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: De Vries
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Yoshinori
  full_name: Fukui, Yoshinori
  last_name: Fukui
- first_name: Alba
  full_name: Juanes Garcia, Alba
  id: 40F05888-F248-11E8-B48F-1D18A9856A87
  last_name: Juanes Garcia
  orcid: 0000-0002-1009-9652
- 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: Dos Reis Rodrigues P, Avellaneda Sarrió M, Canigova N, et al. Migrating immune
    cells globally coordinate protrusive forces. <i>Nature Immunology</i>. 2025;26:1258–1266.
    doi:<a href="https://doi.org/10.1038/s41590-025-02211-w">10.1038/s41590-025-02211-w</a>
  apa: Dos Reis Rodrigues, P., Avellaneda Sarrió, M., Canigova, N., Gärtner, F. R.,
    Vaahtomeri, K., Riedl, M., … Sixt, M. K. (2025). Migrating immune cells globally
    coordinate protrusive forces. <i>Nature Immunology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41590-025-02211-w">https://doi.org/10.1038/s41590-025-02211-w</a>
  chicago: Dos Reis Rodrigues, Patricia, Mario Avellaneda Sarrió, Nikola Canigova,
    Florian R Gärtner, Kari Vaahtomeri, Michael Riedl, Ingrid de Vries, et al. “Migrating
    Immune Cells Globally Coordinate Protrusive Forces.” <i>Nature Immunology</i>.
    Springer Nature, 2025. <a href="https://doi.org/10.1038/s41590-025-02211-w">https://doi.org/10.1038/s41590-025-02211-w</a>.
  ieee: P. Dos Reis Rodrigues <i>et al.</i>, “Migrating immune cells globally coordinate
    protrusive forces,” <i>Nature Immunology</i>, vol. 26. Springer Nature, pp. 1258–1266,
    2025.
  ista: Dos Reis Rodrigues P, Avellaneda Sarrió M, Canigova N, Gärtner FR, Vaahtomeri
    K, Riedl M, de Vries I, Merrin J, Hauschild R, Fukui Y, Juanes Garcia A, Sixt
    MK. 2025. Migrating immune cells globally coordinate protrusive forces. Nature
    Immunology. 26, 1258–1266.
  mla: Dos Reis Rodrigues, Patricia, et al. “Migrating Immune Cells Globally Coordinate
    Protrusive Forces.” <i>Nature Immunology</i>, vol. 26, Springer Nature, 2025,
    pp. 1258–1266, doi:<a href="https://doi.org/10.1038/s41590-025-02211-w">10.1038/s41590-025-02211-w</a>.
  short: P. Dos Reis Rodrigues, M. Avellaneda Sarrió, N. Canigova, F.R. Gärtner, K.
    Vaahtomeri, M. Riedl, I. de Vries, J. Merrin, R. Hauschild, Y. Fukui, A. Juanes
    Garcia, M.K. Sixt, Nature Immunology 26 (2025) 1258–1266.
corr_author: '1'
date_created: 2025-07-27T22:01:26Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2026-04-28T13:26:50Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
- _id: NanoFab
- _id: Bio
doi: 10.1038/s41590-025-02211-w
external_id:
  isi:
  - '001529134300001'
  pmid:
  - '40664976'
file:
- access_level: open_access
  checksum: 0c725123dca7797c682609bff2c4c5ac
  content_type: application/pdf
  creator: dernst
  date_created: 2025-07-31T08:00:33Z
  date_updated: 2025-07-31T08:00:33Z
  file_id: '20096'
  file_name: 2025_NatureImmunology_ReisRodrigues.pdf
  file_size: 13514646
  relation: main_file
  success: 1
file_date_updated: 2025-07-31T08:00:33Z
has_accepted_license: '1'
intvolume: '        26'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 1258–1266
pmid: 1
project:
- _id: bd91e723-d553-11ed-ba76-fe7eeb2185fd
  grant_number: '101071793'
  name: 'Pushing from within: Control of cell shape, integrity and motility by cytoskeletal
    pushing forces'
- _id: c092d618-5a5b-11eb-8a69-f92e1e843fc8
  grant_number: 944-2020
  name: 'Bioelectric patrolling: the role of the local membrane potential in immune
    cell migration'
publication: Nature Immunology
publication_identifier:
  eissn:
  - 1529-2916
  issn:
  - 1529-2908
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/bench-pressing-cells/
  record:
  - id: '20149'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Migrating immune cells globally coordinate protrusive forces
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 26
year: '2025'
...
---
_id: '8142'
abstract:
- lang: eng
  text: Cell production and differentiation for the acquisition of specific functions
    are key features of living systems. The dynamic network of cellular microtubules
    provides the necessary platform to accommodate processes associated with the transition
    of cells through the individual phases of cytogenesis. Here, we show that the
    plant hormone cytokinin fine‐tunes the activity of the microtubular cytoskeleton
    during cell differentiation and counteracts microtubular rearrangements driven
    by the hormone auxin. The endogenous upward gradient of cytokinin activity along
    the longitudinal growth axis in Arabidopsis thaliana roots correlates with robust
    rearrangements of the microtubule cytoskeleton in epidermal cells progressing
    from the proliferative to the differentiation stage. Controlled increases in cytokinin
    activity result in premature re‐organization of the microtubule network from transversal
    to an oblique disposition in cells prior to their differentiation, whereas attenuated
    hormone perception delays cytoskeleton conversion into a configuration typical
    for differentiated cells. Intriguingly, cytokinin can interfere with microtubules
    also in animal cells, such as leukocytes, suggesting that a cytokinin‐sensitive
    control pathway for the microtubular cytoskeleton may be at least partially conserved
    between plant and animal cells.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Takashi Aoyama, David Alabadi, and Bert De Rybel for sharing
  material, Jiří Friml, Maciek Adamowski, and Katerina Schwarzerová for inspiring
  discussions, and Martine De Cock for help in preparing the manuscript. This research
  was supported by the Scientific Service Units (SSUs) of IST Austria through resources
  provided by the Bioimaging Facility (BIF), especially to Robert Hauschild; and the
  Life Science Facility (LSF). J.C.M. is the recipient of a EMBO Long‐Term Fellowship
  (ALTF number 710‐2016). This work was supported with MEYS CR, project no.CZ.02.1.01/0.0/0.0/16_019/0000738
  to J.P., and by the Austrian Science Fund (FWF01_I1774S) to E.B.
article_number: e104238
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Juan C
  full_name: Montesinos López, Juan C
  id: 310A8E3E-F248-11E8-B48F-1D18A9856A87
  last_name: Montesinos López
  orcid: 0000-0001-9179-6099
- first_name: A
  full_name: Abuzeineh, A
  last_name: Abuzeineh
- first_name: Aglaja
  full_name: Kopf, Aglaja
  id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
  last_name: Kopf
  orcid: 0000-0002-2187-6656
- first_name: Alba
  full_name: Juanes Garcia, Alba
  id: 40F05888-F248-11E8-B48F-1D18A9856A87
  last_name: Juanes Garcia
  orcid: 0000-0002-1009-9652
- first_name: Krisztina
  full_name: Ötvös, Krisztina
  id: 29B901B0-F248-11E8-B48F-1D18A9856A87
  last_name: Ötvös
  orcid: 0000-0002-5503-4983
- first_name: J
  full_name: Petrášek, J
  last_name: Petrášek
- 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: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
citation:
  ama: Montesinos López JC, Abuzeineh A, Kopf A, et al. Phytohormone cytokinin guides
    microtubule dynamics during cell progression from proliferative to differentiated
    stage. <i>The Embo Journal</i>. 2020;39(17). doi:<a href="https://doi.org/10.15252/embj.2019104238">10.15252/embj.2019104238</a>
  apa: Montesinos López, J. C., Abuzeineh, A., Kopf, A., Juanes Garcia, A., Ötvös,
    K., Petrášek, J., … Benková, E. (2020). Phytohormone cytokinin guides microtubule
    dynamics during cell progression from proliferative to differentiated stage. <i>The
    Embo Journal</i>. Embo Press. <a href="https://doi.org/10.15252/embj.2019104238">https://doi.org/10.15252/embj.2019104238</a>
  chicago: Montesinos López, Juan C, A Abuzeineh, Aglaja Kopf, Alba Juanes Garcia,
    Krisztina Ötvös, J Petrášek, Michael K Sixt, and Eva Benková. “Phytohormone Cytokinin
    Guides Microtubule Dynamics during Cell Progression from Proliferative to Differentiated
    Stage.” <i>The Embo Journal</i>. Embo Press, 2020. <a href="https://doi.org/10.15252/embj.2019104238">https://doi.org/10.15252/embj.2019104238</a>.
  ieee: J. C. Montesinos López <i>et al.</i>, “Phytohormone cytokinin guides microtubule
    dynamics during cell progression from proliferative to differentiated stage,”
    <i>The Embo Journal</i>, vol. 39, no. 17. Embo Press, 2020.
  ista: Montesinos López JC, Abuzeineh A, Kopf A, Juanes Garcia A, Ötvös K, Petrášek
    J, Sixt MK, Benková E. 2020. Phytohormone cytokinin guides microtubule dynamics
    during cell progression from proliferative to differentiated stage. The Embo Journal.
    39(17), e104238.
  mla: Montesinos López, Juan C., et al. “Phytohormone Cytokinin Guides Microtubule
    Dynamics during Cell Progression from Proliferative to Differentiated Stage.”
    <i>The Embo Journal</i>, vol. 39, no. 17, e104238, Embo Press, 2020, doi:<a href="https://doi.org/10.15252/embj.2019104238">10.15252/embj.2019104238</a>.
  short: J.C. Montesinos López, A. Abuzeineh, A. Kopf, A. Juanes Garcia, K. Ötvös,
    J. Petrášek, M.K. Sixt, E. Benková, The Embo Journal 39 (2020).
corr_author: '1'
date_created: 2020-07-21T09:08:38Z
date_published: 2020-09-01T00:00:00Z
date_updated: 2025-04-15T06:37:27Z
day: '01'
ddc:
- '580'
department:
- _id: MiSi
- _id: EvBe
doi: 10.15252/embj.2019104238
external_id:
  isi:
  - '000548311800001'
  pmid:
  - '32667089'
file:
- access_level: open_access
  checksum: 43d2b36598708e6ab05c69074e191d57
  content_type: application/pdf
  creator: dernst
  date_created: 2020-12-02T09:13:23Z
  date_updated: 2020-12-02T09:13:23Z
  file_id: '8827'
  file_name: 2020_EMBO_Montesinos.pdf
  file_size: 3497156
  relation: main_file
  success: 1
file_date_updated: 2020-12-02T09:13:23Z
has_accepted_license: '1'
intvolume: '        39'
isi: 1
issue: '17'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 253E54C8-B435-11E9-9278-68D0E5697425
  grant_number: ALTF710-2016
  name: Molecular mechanism of auxindriven formative divisions delineating lateral
    root organogenesis in plants
- _id: 2542D156-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I 1774-B16
  name: Hormone cross-talk drives nutrient dependent plant development
publication: The Embo Journal
publication_identifier:
  eissn:
  - 1460-2075
  issn:
  - 0261-4189
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Phytohormone cytokinin guides microtubule dynamics during cell progression
  from proliferative to differentiated stage
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 39
year: '2020'
...
