A role of small GTPases in the formation of neural network system

神经丛蛋白是轴突导向分子信号素的受体。我们最近报道了Sema4D受体Plexin-B1通过R-RAS间隙活性抑制PI3激酶信号，导致生长锥体塌陷。PIP3水平受PI3激酶和PTEN的调控。我们随后发现，Sema4D/Plexin-B1抑制PI3激酶活性，但刺激PTEN活性，导致Akt活性抑制，GSK3b激活和CRMP-2磷酸化，从而促进海马神经元生长锥的崩溃。另一方面，R-RAS亚家族的另一个成员M-RAS的表达在树突发育过程中上调，M-RAS是反晶生长所必需的。Sema4D/Plexin-B1显示M-RAS GAP活性，并通过M-RAS GAP活性抑制枝晶生长。因此，Plexin-B1是R-RAS和M-RAS的双重功能缺口，分别重塑轴突和树突的形态。

Plexins are receptors for axonal guidance molecules semaphorins. We recently reported thet the Sema4D receptor, Plexin-B1, suppresses PI3 kinase signaling through R-Ras GAP activity, inducing growth cone collapse. PIP3 level is critically regulated by PI3 kinase and PTEN. We then revealed that Sema4D/Plexin-B1 suppresses PI3 kinase activity but stimulates PTEN activity, leading to Akt activity suppression, GSK3b activation and CRMP-2 phosphorylation and then promotes growth cone collapse in hippocampal neurons. On the other hand, the expression of M-Ras, another member of R-Ras subfamily, is upregulated during dendritic development, and M-Ras is required for the denrite outgrowth. Sema4D/Plexin-B1 shows M-Ras GAP activity and suppresses dendrite outgrowth through M-Ras GAP acitivty. Thus, Plexin-B1 is a dual functional GAP for R-Ras and M-Ras, remodeling axon and dendrite morphology, respectively.