Key Laboratory of Molecular and Developmental Biology, Center for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
J Biol Chem. 2010 Nov 5;285(45):35133-41. doi: 10.1074/jbc.M110.153429. Epub 2010 Sep 1.
The Slit-Robo GTPase-activating proteins (srGAPs) are critical for neuronal migration through inactivation of Rho GTPases Cdc42, Rac1, and RhoA. Here we report that srGAP2 physically interacts with protein arginine methyltransferase 5 (PRMT5). srGAP2 localizes to the cytoplasm and plasma membrane protrusion. srGAP2 knockdown reduces cell adhesion spreading and increases cell migration, but has no effect on cell proliferation. PRMT5 binds to the N terminus of srGAP2 (225-538 aa) and methylates its C-terminal arginine residue Arg-927. The methylation mutant srGAP2-R927A fails to rescue the cell spreading rate, is unable to localize to the plasma membrane leading edge, and perturbs srGAP2 homodimer formation mediated by the F-BAR domain. These results suggest that srGAP2 arginine methylation plays important roles in cell spreading and cell migration through influencing membrane protrusion.
Slit-Robo GTPase 激活蛋白（srGAPs）通过失活 Rho GTPases Cdc42、Rac1 和 RhoA，对于神经元迁移至关重要。在这里，我们报告 srGAP2 与蛋白质精氨酸甲基转移酶 5（PRMT5）发生物理相互作用。srGAP2 定位于细胞质和质膜突起。srGAP2 敲低会降低细胞黏附扩展并增加细胞迁移，但对细胞增殖没有影响。PRMT5 结合到 srGAP2 的 N 端（225-538aa）并甲基化其 C 端精氨酸残基 Arg-927。甲基化突变体 srGAP2-R927A 不能挽救细胞扩展速率，无法定位到质膜前缘，并扰乱由 F-BAR 结构域介导的 srGAP2 同源二聚体形成。这些结果表明，srGAP2 精氨酸甲基化通过影响质膜突起在细胞扩展和细胞迁移中发挥重要作用。
