Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration.
Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration.
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DOI：
10.1083/jcb.201002067
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发表时间：
2010-08-23
期刊：
影响因子：
--
通讯作者：
Ridley AJ
中科院分区：
文献类型：
--
作者：
Heasman SJ;Carlin LM;Cox S;Ng T;Ridley AJ
RhoA GTdR的生物传感器说明了其在迁移淋巴细胞的前部和后部的激活模式。经内皮细胞迁移（TEM）是一个严格调控的过程，白细胞从血管系统迁移到组织中。Rho鸟苷三磷酸酶（GTP酶）与TEM有关，但Rho家族成员的贡献尚不清楚。在这项研究中，我们使用RNA干扰筛选，以确定哪些Rho GTPases影响T细胞TEM，并证明RhoA是这个过程中的关键。RhoA耗竭导致迁移极性丧失;细胞缺乏前缘和尾足结构，相反，具有稳定的狭窄突起，具有离域突起和收缩。通过成像的RhoA活性生物传感器在transmigrating T细胞，我们发现，RhoA是局部和动态激活的前沿，其激活之前的延伸和收缩事件，并在尾足，在那里它是与ROCK介导的收缩。Rho鸟嘌呤核苷酸交换因子（GEF）GEF-H1有助于尾足收缩，但不影响前缘。我们的数据表明，RhoA活性在T细胞的前部和后部动态调节以协调TEM。
A biosensor for the RhoA GTPase illustrates its activation patterns in both the front and rear of migrating lymphocytes. 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.
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DOI：
10.1083/jcb.200112126
发表时间：
2002-06-24
期刊：
The Journal of cell biology
影响因子：
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