Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Genetically Modified
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Axons / ultrastructure
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Body Patterning / genetics
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Body Patterning / physiology
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Drosophila / embryology
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Drosophila / genetics
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Drosophila / metabolism
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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GTPase-Activating Proteins / genetics
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GTPase-Activating Proteins / metabolism*
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Genes, Insect
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In Vitro Techniques
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Nerve Net / embryology
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Nerve Net / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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RNA Interference
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Roundabout Proteins
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Signal Transduction
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism
Substances
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Drosophila Proteins
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GTPase-Activating Proteins
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Nerve Tissue Proteins
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Receptors, Immunologic
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rac GTP-Binding Proteins