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

Takesono, A; Heasman, SJ; Wojciak-Stothard, B; Garg, R; Ridley, AJ; (2010) Microtubules Regulate Migratory Polarity through Rho/ROCK Signaling in T Cells. PLOS ONE , 5 (1) , Article e8774. 10.1371/journal.pone.0008774. Green open access

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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.

Type: Article
Title: Microtubules Regulate Migratory Polarity through Rho/ROCK Signaling in T Cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0008774
Publisher version: http://dx.doi.org/10.1371/journal.pone.0008774
Language: English
Additional information: © 2010 Takesono et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by Biotechnology and Biological Sciences Research Council (BBSRC) grant 31/C14420, Leukaemia Research Fund United Kingdom grant 04021 and Cancer Research United Kingdom grant C6620/A8833. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: NEUTROPHIL POLARIZATION, ACTIN CYTOSKELETON, ALPHA-TUBULIN, RHO-GTPASES, IN-VIVO, CHEMOTAXIS, MOTILITY, LYMPHOCYTES, DYNAMICS, MYOSIN
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/136236
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