Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion
Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion
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DOI：
10.1073/pnas.0409325102
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发表时间：
2005-03-22
影响因子：
11.1
通讯作者：
Bashaw, GJ
中科院分区：
文献类型：
--
作者：
Hu, HL;Li, M;Bashaw, GJ
Rho家族GTP酶的调节因子GTP酶激活蛋白(GAP)和鸟嘌呤交换因子(GEF)在轴突引导中起着重要作用。通过对果蝇Rho家族GEF和GAP的功能基因组研究，我们已经确定了Rho家族的GAP CrossGAP(CrGAP)，它参与了ROBO受体介导的排斥性轴突引导。CrGAP在物理上与Robo受体相关。CrGAP活性过高或过低都会导致ROBO介导的中线选择点的排斥力出现缺陷。CrGAP的功能获得表型模仿了Robo和RAC的功能丧失表型。CrGAP、Robo和RAC之间剂量敏感的遗传相互作用支持一种模型，在该模型中，CrGAP通过传递Robo受体下游的信号来调节RAC依赖的细胞骨架变化。
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.