SrGAP3 interacts with lamellipodin at the cell membrane and regulates Rac-dependent cellular protrusions

被引：37

作者：

Endris, Volker ^{[1
]}

Haussmann, Lydia ^{[1
]}

Buss, Elena ^{[1
]}

Bacon, Claire ^{[1
]}

Bartsch, Dusan ^{[2
,3
]}

Rappold, Gudrun ^{[1
]}

机构：

[1] Heidelberg Univ, Dept Human Mol Genet, D-6800 Mannheim, Germany

[2] Cent Inst Mental Hlth, Dept Mol Biol, D-6800 Mannheim, Germany

[3] Heidelberg Univ, Mannheim Med Fac, D-6800 Mannheim, Germany

来源：

JOURNAL OF CELL SCIENCE | 2011年 / 124卷 / 23期

关键词：

Actin dynamics; F-BAR; Focal adhesions; Slit-Robo signaling; F-BAR DOMAIN; AXON GUIDANCE; SIGNAL-TRANSDUCTION; NEURONAL MIGRATION; ACTIN CYTOSKELETON; ENA/VASP PROTEINS; SLIT PROTEINS; KINASE; RHO; ACTIVATION;

D O I：

10.1242/jcs.077081

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

SrGAP3/MEGAP is a member of the Slit-Robo GAP (srGAP) family and is implicated in repulsive axon guidance and neuronal migration through Slit-Robo-mediated signal transduction. Here we describe an inhibitory role of srGAP3 on actin dynamics, specifically on lamellipodia formation. We show that the F-BAR domain localizes srGAP3 to the leading edge of cellular protrusions whereas the SH3 domain is important for focal adhesion targeting. We report on a novel srGAP3 interaction partner, lamellipodin, which localizes with srGAP3 at the leading edge. Live-cell analyses revealed that srGAP3 influences lamellipodin-evoked lamellipodial dynamics. Furthermore, we show that mouse embryonic fibroblasts derived from homozygous srGAP3-knockout embryos display an increased cell area and lamellipodia formation that can be blocked by shRNA-mediated knockdown of lamellipodin.

引用

页码：3941 / 3955

页数：15

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