A role of interactive actions of small GTPases in the formation of neural network

小分子GTP酶在神经网络的形成，尤其是轴突的引导中起着重要作用。我们最近报道，Sema4D受体Plexin-B1通过R-RAS间隙活性抑制PI3激酶信号，导致生长锥体崩溃。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。Sema4D/Plexin-B1通过R-RAS间隙活性抑制ECM依赖的R-RAS激活和R-RAS介导的整合素激活。我们还发现，R-RAS与MYO7A结合并刺激其运动活性，促进整合素运输到质膜前沿，然后诱导产生整合素激活。我们认为Sema4D/Plexin-B1抑制R-RAS介导的MYO7A刺激和将整合素运输到质膜，导致整合素失活和随后的轴突排斥。

Small GTPases play important roles in the formation of neural network, especially axon guidance. We recently reported that the Sema4D receptor, Plexin-B1, suppresses PI3 kinase signaling through R-Ras GAP activity, inducing growth cone collapse. 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. Sema4D/Plexin-B1 suppresses the ECM-dependent R-Ras activation and R-Ras-mediated integrin activation through R-Ras GAP activity. We also revealed that R-Ras binds to Myo7a and stimulates its motor activity, promoting trafficking integrin to the leading edge of plasma membrane and then induces resultant integrin activation. We here propose that Sema4D/Plexin-B1 suppresses R-Ras-mediated Myo7a stimulation and trafficking integrin to the plasma membrane, leading to integrin inactivation and subsequent axon repulsion.