SrGAP3 interacts with lamellipodin at the cell membrane and regulates Rac-dependent cellular protrusions
SrGAP3 interacts with lamellipodin at the cell membrane and regulates Rac-dependent cellular protrusions
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DOI：
10.1242/jcs.077081
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发表时间：
2011-12-01
影响因子：
4
通讯作者：
Rappold, Gudrun
中科院分区：
文献类型：
--
作者：
Endris, Volker;Haussmann, Lydia;Rappold, Gudrun
SrGAP3/MEGAP 是 Slit-Robo GAP (srGAP) 家族的成员，通过 Slit-Robo 介导的信号转导参与排斥性轴突引导和神经元迁移。在这里，我们描述了 srGAP3 对肌动蛋白动力学的抑制作用，特别是对片状伪足形成的抑制作用。我们发现 F-BAR 结构域将 srGAP3 定位于细胞突起的前缘，而 SH3 结构域对于粘着斑靶向很重要。我们报告了一种新型 srGAP3 相互作用伙伴，lamellipodin，其定位于 srGAP3 的前沿。活细胞分析表明 srGAP3 影响板脂蛋白诱发的板状足动力学。此外，我们还发现，源自纯合 srGAP3 敲除胚胎的小鼠胚胎成纤维细胞显示出细胞面积和片状伪足形成的增加，这可以通过 shRNA 介导的片状脂质敲低来阻断。
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.