期刊
JOURNAL OF CELL BIOLOGY
卷 190, 期 4, 页码 553-563出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201002067
关键词
-
类别
资金
- Medical Research Council
- Bettencourt-Schueller Foundation
- Leukaemia Research Fund
- Engineering and Physical Sciences Research Council
- Richard Dimbleby Cancer Fund
- Medical Research Council [G0600806] Funding Source: researchfish
- MRC [G0600806] Funding Source: UKRI
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据