Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Nat Commun. 2013;4:2005. doi: 10.1038/ncomms3005.
Polarized membrane addition is crucial for axon development and elongation during neuronal morphogenesis. This process is believed to be regulated by directed membrane trafficking of Rab10-containing post-Golgi carriers. However, the mechanisms underlying the biogenesis of these carriers remain unclear. Here, we report that Rab10 interaction with myosin Vb (MYO5B) determines the formation of Rab10 carriers and is important for axon development. Rab10 interacts with the exon D-encoded domain of MYO5B. Downregulating the expression of MYO5B (+D) or blocking its interaction with Rab10 impairs the fission of Rab10 vesicles from trans-Golgi membranes, causes a decrease in the number of Rab10 transport carriers and inhibits axon development in cultured hippocampal neurons. Furthermore, the MYO5B-Rab10 system is required for axon development of vertebrate neocortical neurons or zebrafish retinal ganglion cells in vivo. Thus, specific interaction between Rab10 and MYO5B controls the formation of Rab10 vesicles, which is required for axon development.
极化膜的添加对于神经元形态发生过程中的轴突发育和伸长至关重要。据信,这个过程受到含有 Rab10 的高尔基体后膜载体的定向膜运输的调节。然而,这些载体生物发生的机制仍不清楚。在这里,我们报告 Rab10 与肌球蛋白 VB(MYO5B)的相互作用决定了 Rab10 载体的形成,并且对轴突发育很重要。Rab10 与 MYO5B 的外显子 D 编码结构域相互作用。下调 MYO5B(+D)的表达或阻断其与 Rab10 的相互作用会损害 Rab10 从反式高尔基体膜中出芽的能力,导致 Rab10 运输载体的数量减少,并抑制培养的海马神经元中的轴突发育。此外,MYO5B-Rab10 系统对于体内脊椎动物新皮层神经元或斑马鱼视网膜神经节细胞的轴突发育是必需的。因此,Rab10 和 MYO5B 之间的特异性相互作用控制 Rab10 囊泡的形成,这对于轴突发育是必需的。