期刊
JOURNAL OF CELL SCIENCE
卷 124, 期 23, 页码 3941-3955出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.077081
关键词
Actin dynamics; F-BAR; Focal adhesions; Slit-Robo signaling
类别
资金
- Deutsche Forschungsgesellschaft [SFB488, graduate college GK791]
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.
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