SrGAP3 interacts with lamellipodin at the cell membrane and regulates Rac-dependent cellular protrusions
- 1 December 2011
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 124 (23), 3941-3955
- https://doi.org/10.1242/jcs.077081
Abstract
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.Keywords
This publication has 52 references indexed in Scilit:
- WRP/srGAP3Facilitates the Initiation of Spine Development by an Inverse F-BAR Domain, and Its Loss Impairs Long-Term MemoryJournal of Neuroscience, 2011
- c-Abl, Lamellipodin, and Ena/VASP Proteins Cooperate in Dorsal Ruffling of Fibroblasts and Axonal MorphogenesisCurrent Biology, 2010
- Cytoskeletal dynamics in growth-cone steeringJournal of Cell Science, 2009
- The F-BAR Domain of srGAP2 Induces Membrane Protrusions Required for Neuronal Migration and MorphogenesisCell, 2009
- Contributions of F-BAR and SH2 Domains of Fes Protein Tyrosine Kinase for Coupling to the FcεRI Pathway in Mast CellsMolecular and Cellular Biology, 2009
- Spatial mapping of the neurite and soma proteomes reveals a functional Cdc42/Rac regulatory networkProceedings of the National Academy of Sciences, 2008
- Ena/VASP: proteins at the tip of the nervous systemCurrent Opinion in Neurobiology, 2008
- The Phosphorylation of Myosin II at the Ser1 and Ser2 Is Critical for Normal Platelet-derived Growth Factor–induced Reorganization of Myosin FilamentsMolecular Biology of the Cell, 2007
- Ena/VASP Proteins Have an Anti-Capping Independent Function in Filopodia FormationMolecular Biology of the Cell, 2007
- MEGAP impedes cell migration via regulating actin and microtubule dynamics and focal complex formationExperimental Cell Research, 2006