Vogt D L, Gray C D, Young W S, Orellana S A, Malouf A T
Department of Neurosciences, Case Western Reserve University, 11100 Euclid Ave., Cleveland, OH 44106, USA.
Mol Cell Neurosci. 2007 Nov;36(3):332-42. doi: 10.1016/j.mcn.2007.07.004. Epub 2007 Jul 24.
This report examines the structure and function of ARHGAP4, a novel RhoGAP whose structural features make it ideally suited to regulate the cytoskeletal dynamics that control cell motility and axon outgrowth. Our studies show that ARHGAP4 inhibits the migration of NIH/3T3 cells and the outgrowth of hippocampal axons. ARHGAP4 contains an N-terminal FCH domain, a central GTPase activating (GAP) domain and a C-terminal SH3 domain. Our structure/function analyses show that the FCH domain appears to be important for spatially localizing ARHGAP4 to the leading edges of migrating NIH/3T3 cells and to axon growth cones. Our analyses also show that the GAP domain and C-terminus are necessary for ARHGAP4-mediated inhibition of cell and axon motility. These observations suggest that ARHGAP4 can act as a potent inhibitor of cell and axon motility when it is localized to the leading edge of motile cells and axons.
本报告研究了ARHGAP4的结构与功能，ARHGAP4是一种新型的RhoGAP，其结构特征使其非常适合调节控制细胞运动和轴突生长的细胞骨架动力学。我们的研究表明，ARHGAP4抑制NIH/3T3细胞的迁移以及海马轴突的生长。ARHGAP4包含一个N端FCH结构域、一个中央GTP酶激活（GAP）结构域和一个C端SH3结构域。我们的结构/功能分析表明，FCH结构域对于将ARHGAP4在空间上定位到迁移的NIH/3T3细胞的前沿以及轴突生长锥似乎很重要。我们的分析还表明，GAP结构域和C端对于ARHGAP4介导的细胞和轴突运动抑制是必需的。这些观察结果表明，当ARHGAP4定位于运动细胞和轴突的前沿时，它可以作为细胞和轴突运动的有效抑制剂。
