Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion.
The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila, we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout (Robo) receptor-mediated repulsive axon guidance. CrGAP physically associates with the Robo receptor. Too much or too little CrGAP activity leads to defects in Robo-mediated repulsion at the midline choice point. The CrGAP gain-of-function phenotype mimics the loss-of-function phenotypes of both Robo and Rac. Dosage-sensitive genetic interactions among CrGAP, Robo, and Rac support a model in which CrGAP transduces signals downstream of Robo receptor to regulate Rac-dependent cytoskeletal changes.
Hu
Hailan
H
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Li
Ming
M
Labrador
Juan-Pablo
JP
McEwen
Jason
J
Lai
Eric C
EC
Goodman
Corey S
CS
Bashaw
Greg J
GJ
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000648:ultrastructure; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D017344:Genes, Insect; D066298:In Vitro Techniques; D009415:Nerve Net / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D020744:rac GTP-Binding Proteins; D000097905:Roundabout Proteins