Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration

Heasman, S. J., Carlin, L. M. , Cox, S., Ng, T. and Ridley, A. J. (2010) Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration. Journal of Cell Biology, 190(4), pp. 553-563. (doi: 10.1083/jcb.201002067) (PMID:20733052) (PMCID:PMC2928012)

Abstract

Transendothelial migration (TEM) is a tightly regulated process whereby leukocytes migrate from the vasculature into tissues. Rho guanosine triphosphatases (GTPases) are implicated in TEM, but the contributions of individual Rho family members are not known. In this study, we use an RNA interference screen to identify which Rho GTPases affect T cell TEM and demonstrate that RhoA is critical for this process. RhoA depletion leads to loss of migratory polarity; cells lack both leading edge and uropod structures and, instead, have stable narrow protrusions with delocalized protrusions and contractions. By imaging a RhoA activity biosensor in transmigrating T cells, we find that RhoA is locally and dynamically activated at the leading edge, where its activation precedes both extension and retraction events, and in the uropod, where it is associated with ROCK-mediated contraction. The Rho guanine nucleotide exchange factor (GEF) GEF-H1 contributes to uropod contraction but does not affect the leading edge. Our data indicate that RhoA activity is dynamically regulated at the front and back of T cells to coordinate TEM.

• Item Type: Articles
• Additional Information: This work was funded by the Medical Research Council (A.J. Ridley), the Bettencourt-Schueller Foundation (A.J. Ridley), the Leukaemia Research Fund (A.J. Ridley), Engineering and Physical Sciences Research Council (L. Carlin; T. Ng), and the Richard Dimbleby Cancer Fund (T. Ng).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Carlin, Dr Leo
• Authors: Heasman, S. J., Carlin, L. M., Cox, S., Ng, T., and Ridley, A. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Cell Biology
• Publisher: Rockefeller University Press
• ISSN: 0021-9525
• ISSN (Online): 1540-8140
• Copyright Holders: Copyright © 2010 Heasman et al.
• First Published: First published in Journal of Cell Biology 190(4):533-563
• Publisher Policy: Reproduced under a Creative Commons license