RA-RhoGAP, Rap-activated Rho GTPase-activating Protein Implicated in Neurite Outgrowth through Rho*♦
RA-RhoGAP, Rap-activated Rho GTPase-activating Protein Implicated in Neurite Outgrowth through Rho*♦
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DOI：
10.1074/jbc.m504587200
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发表时间：
2005-09
影响因子：
4.8
通讯作者：
Tomohiro Yamada;T. Sakisaka;S. Hisata;T. Baba;Y. Takai
中科院分区：
文献类型：
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作者：
Tomohiro Yamada;T. Sakisaka;S. Hisata;T. Baba;Y. Takai
Rap 1和Rho小G蛋白参与了神经突起的生长，但Rap 1和Rho在神经突起生长中的功能关系仍有待建立。在这里，我们确定了一个有效的Rho GTP酶激活蛋白（GAP），RA-RhoGAP，作为Rap 1在神经突生长的直接下游目标。RA-RhoGAP具有RA和GAP结构域，并显示出对Rho具有特异性的GAP活性，该活性通过Rap 1的GTP结合活性形式与RA结构域的结合而增强。RA-RhoGAP的过表达诱导Rho的失活，以Rap 1依赖的方式促进神经突起的生长。RA-RhoGAP的敲除减少了Rap 1诱导的神经突生长。这些结果表明，RA-RhoGAP从Rap 1到Rho的信号转导和调节神经突起的生长。
Rap1 and Rho small G proteins have been implicated in the neurite outgrowth, but the functional relationship between Rap1 and Rho in the neurite outgrowth remains to be established. Here we identified a potent Rho GTPase-activating protein (GAP), RA-RhoGAP, as a direct downstream target of Rap1 in the neurite outgrowth. RA-RhoGAP has the RA and GAP domains and showed GAP activity specific for Rho, which was enhanced by the binding of the GTP-bound active form of Rap1 to the RA domain. Overexpression of RA-RhoGAP induced inactivation of Rho for promoting the neurite outgrowth in a Rap1-dependent manner. Knockdown of RA-RhoGAP reduced the Rap1-induced neurite outgrowth. These results indicate that RA-RhoGAP transduces a signal from Rap1 to Rho and regulates the neurite outgrowth.