title: SrGAP3 interacts with lamellipodin at the cell membrane and regulates Rac-dependent cellular protrusions.
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.
authors.affiliation: Department of Human Molecular Genetics, University of Heidelberg,  Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Endris
authors.forename: Lydia
authors.initials: L
authors.lastname: Haussmann
authors.forename: Elena
authors.initials: E
authors.lastname: Buss
authors.forename: Claire
authors.initials: C
authors.lastname: Bacon
authors.forename: Dusan
authors.initials: D
authors.lastname: Bartsch
authors.forename: Gudrun
authors.initials: G
authors.lastname: Rappold
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein; D018909:src Homology Domains
chemical_list: D000199:Actins; D020690:GTPase-Activating Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; C465659:SRGAP3 protein, human; C516731:Srgap3 protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein