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Cited by 170Cellular Mechanics and InteractionsMicrotubule and mitosis dynamicsProtein Kinase Regulation and GTPase Signaling

Microtubules Regulate Migratory Polarity through Rho/ROCK Signaling in T Cells

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Takesono, Aya, Heasman, Sarah J., Wojciak-Stothard, Beata, Garg, Ritu, Ridley, Anne J.·2010·PLoS ONE
DOI 10.1371/journal.pone.0008774PMC PMC2808253
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Abstract

BACKGROUND: Migrating leukocytes normally have a polarized morphology with an actin-rich lamellipodium at the front and a uropod at the rear. Microtubules (MTs) are required for persistent migration and chemotaxis, but how they affect cell polarity is not known. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that T cells treated with nocodazole to disrupt MTs are unable to form a stable uropod or lamellipodium, and instead often move by membrane blebbing with reduced migratory persistence. However, uropod-localized receptors and ezrin/radixin/moesin proteins still cluster in nocodazole-treated cells, indicating that MTs are required specifically for uropod stability. Nocodazole stimulates RhoA activity, and inhibition of the RhoA target ROCK allows nocodazole-treated cells to re-establish lamellipodia and uropods and persistent migratory polarity. ROCK inhibition decreases nocodazole-induced membrane blebbing and stabilizes MTs. The myosin inhibitor blebbistatin also stabilizes MTs, indicating that RhoA/ROCK act through myosin II to destabilize MTs. CONCLUSIONS/SIGNIFICANCE: Our results indicate that RhoA/ROCK signaling normally contributes to migration by affecting both actomyosin contractility and MT stability. We propose that regulation of MT stability and RhoA/ROCK activity is a mechanism to alter T-cell migratory behavior from lamellipodium-based persistent migration to bleb-based migration with frequent turning.

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  • Abrogation of the transmission of the GEF-H1-dependent increase in contractility, for example, by ROCK inhibition, suppresses membrane blebbing and restores lamellipodial polarity.

    “Our data concur with a previous report showing that abrogation of the transmission of the GEF‐H1‐dependent increase in contractility, for example, by ROCK inhibition, suppresses membrane blebbing and restores lamellipodial polarity [64].”

    From Paclitaxel induces <scp>NM2</scp> ‐dependent cellular contraction through <scp>GEF</scp> ‐ <scp>H1</scp> dissociation from microtubules and <scp>RhoA</scp> / <scp>ROCK</scp> activation in cancer cells (2026) · cites this paper as [64]

    The Results section, “ROCK Inhibition Prevents Blebbing and Restores Migratory Polarity in Nocodazole-Treated Cells,” reports that ROCK inhibition suppressed blebbing and restored lamellipodial polarity. However, the Discussion’s Figure 10 model refers only to an unnamed RhoGEF, and our copy does not establish that the increase in contractility in these cells is GEF-H1-dependent. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Takesono, A., Heasman, S. J., Wojciak-Stothard, B., Garg, R., & Ridley, A. J.
Affiliations
  • University of Exeter (GB)
  • King's College London (GB)
Corresponding author
Ridley, Anne J.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-01-19
Volume
5
Issue
1
Pages
e8774
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0008774
PMC
PMC2808253
OpenAlex
W2095404261
Cited by
170
References
4
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 12 · 2020: 10 · 2019: 11 · 2018: 11 · 2017: 14 · 2016: 5 · 2015: 12 · 2014: 16 · 2013: 17 · 2012: 15
FWCI
7.84
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Research Portal (King's College London) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
  • Cancer Research UK (C6620-A8833)
  • University of Exeter
  • Blood Cancer UK (04021)
  • Directorate for Biological Sciences
  • Biotechnology and Biological Sciences Research Council (31/C14420)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
microtubules, T cell migration, cell polarity, uropod, lamellipodia, RhoA/ROCK signaling, nocodazole, membrane blebbing, ezrin/radixin/moesin, myosin II, actomyosin contractility, chemotaxis, blebbistatin
MeSH terms
Humans, Microtubules, T-Lymphocytes, Signal Transduction, Nocodazole, Cell Polarity, rhoA GTP-Binding Protein, Cell Line, Tumor, rho-Associated Kinases

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