Different Requirement for Rnd GTPases of R-Ras GAP Activity of Plexin-C1 and Plexin-D1
Different Requirement for Rnd GTPases of R-Ras GAP Activity of Plexin-C1 and Plexin-D1
复制标题
DOI：
10.1074/jbc.m805213200
复制
发表时间：
2009-03-13
影响因子：
4.8
通讯作者：
Negishi, Manabu
中科院分区：
文献类型：
--
作者：
Uesugi, Kanami;Oinuma, Izumi;Negishi, Manabu
丛蛋白由丛蛋白-A、-B、-C和-D四个亚家族组成，是调节细胞黏附、迁移和轴突引导的信号素受体。在丛蛋白亚家族中，丛蛋白-A1和丛蛋白-B1作为R-RAS间隙发挥作用，诱导排斥反应，而R-RAS间隙活性的表达需要Rho GTP酶RND亚家族成员RND1的结合。然而，Plexin-D_1和Plexin-C_1的信号通路仍然不清楚。在这里，我们发现Plexin-D1显示了R-RAS间隙活性，并抑制了COS-7细胞的迁移，而这些作用需要另一个RND亚家族GTP酶RND2。RND2与皮层神经元中的丛状蛋白-D1结合，Sema3E/Plexin-D1诱导的抑制皮质神经元轴突生长需要RND2和下调R-RAS活性。另一方面，Plexin-C1显示R-RAS GAP活性，并抑制无RND蛋白的COS-7细胞的迁移。因此，R-RAS GAP活性是丛状蛋白亚家族的共同功能，但RND蛋白对丛状蛋白的R-RAS间隙活性的调节在丛状蛋白亚家族中是不同的。
Plexins, comprising Plexin-A, -B, -C, and -D subfamilies, are receptors for semaphorins governing cell adhesion, migration, and axon guidance. Among plexin subfamilies, Plexin-A1 and Plexin-B1 have been shown to function as an R-Ras GAP, inducing repulsive responses, and the expression of R-Ras GAP activity requires the binding of Rnd1, a member of Rnd subfamily of Rho GTPases. However, signaling pathways of Plexin-D1 and Plexin-C1 still remain obscure. Here, we found that Plexin-D1 displayed R-Ras GAP activity and inhibited migration of COS-7 cells, and these actions required Rnd2, another Rnd subfamily GTPase. Rnd2 bound to Plexin-D1 in cortical neurons, and Sema3E/Plexin-D1-induced inhibition of axon outgrowth of cortical neurons required Rnd2 and down-regulation of R-Ras activity. On the other hand, Plexin-C1 displayed R-Ras GAP activity and inhibited cell migration of COS-7 cells without Rnd proteins. Therefore, R-Ras GAP activity is a common function of plexin subfamilies but the regulation of R-Ras GAP activity of plexins by Rnd proteins is different among plexin subfamilies.