Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth
Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth
复制标题
神经元 GAP-Porf-2 转导 EphB1 信号以抑制轴突生长
DOI：
10.1007/s00018-018-2858-0
复制
发表时间：
2018-11-01
影响因子：
8
通讯作者：
Feng, Dong-Fu
中科院分区：
文献类型：
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作者：
Huang, Guo-Hui;Guo, Lin;Feng, Dong-Fu
轴突生长和引导需要大量的细胞外信号和细胞内介质，这些信号转导生长锥中的信号来调节细胞骨架的动力学。然而，细胞骨架效应器对这些信号的反应方式仍然难以捉摸。在这里，我们证明了PORF-2，一种神经元表达的RhoGTP酶激活蛋白，通过以细胞自主的方式限制生长锥的扩张，在抑制初始轴突生长方面发挥了重要作用。此外，EphB1受体被认为是一种上游控制因子，可以结合和调节Pporf-2，特别是在细胞外Ephin-B的刺激下。激活的EphB正向信号通过PORF-2的GAP结构域使rac1失活，从而抑制生长锥体的形成并阻止轴突的生长。因此，我们的结果提供了一种新的GAP，通过Eph受体非依赖和Eph受体依赖的途径来调节轴突的生长和制动。
Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone formation and brakes axon growth. Our results therefore provide a novel GAP that regulates axon growth and braking sequentially through Eph receptor-independent and Eph receptor-dependent pathways.