FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling

被引：303

作者：

Ohta, Yasutaka ^{[1
]}

Hartwig, John H. ^{[1
]}

Stossel, Thomas P. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Hematol Div, Boston, MA 02115 USA

来源：

NATURE CELL BIOLOGY | 2006年 / 8卷 / 08期

关键词：

D O I：

10.1038/ncb1437

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

FilGAP is a newly recognized filamin A ( FLNa)-binding RhoGTPase-activating protein. The GTPase-activating protein ( GAP) activity of FilGAP is specific for Rac and FLNa binding targets FilGAP to sites of membrane protrusion, where it antagonizes Rac in vivo. Dominant-negative FilGAP constructs lacking GAP activity or knockdown of endogenous FilGAP by small interference RNA ( siRNA) induce spontaneous lamellae formation and stimulate cell spreading on fibronectin. Knockdown of endogenous FilGAP abrogates ROCK-dependent suppression of lamellae. Conversely, forced expression of FilGAP induces numerous blebs around the cell periphery and a ROCK-specific inhibitor suppresses bleb formation. ROCK phosphorylates FilGAP, and this phosphorylation stimulates its RacGAP activity and is a requirement for FilGAP-mediated bleb formation. FilGAP is, therefore, a mediator of the well-established antagonism of Rac by RhoA that suppresses leading edge protrusion and promotes cell retraction to achieve cellular polarity.

引用

页码：803 / U35

页数：16

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