Vangl2 acts at the interface between actin and N-cadherin to modulate mammalian neuronal outgrowth
Vangl2 acts at the interface between actin and N-cadherin to modulate mammalian neuronal outgrowth
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DOI：
10.7554/elife.51822
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发表时间：
2020-01-07
期刊：
影响因子：
7.7
通讯作者：
Montcouquiol, Mireille
中科院分区：
文献类型：
--
作者：
Carvalho, Steve Dos-Santos;Moreau, Maite M.;Montcouquiol, Mireille
粘附复合物和细胞骨架之间的动态机械相互作用对于轴突生长和引导是必不可少的。是否平面细胞极性（PCP）蛋白，调节细胞骨架动力学，并出现必要的一些轴突的指导，也介导与膜粘附的相互作用仍不清楚。在这里，我们表明，Vangl 2控制生长锥的速度，通过调节内部的逆行肌动蛋白流的N-钙粘蛋白依赖的方式。单分子追踪实验表明，Vangl 2的丢失减少了快速扩散的N-钙粘蛋白膜分子，并增加了受限的N-钙粘蛋白轨迹。使用光学操纵的N-钙粘蛋白涂层微球，我们相关的N-钙粘蛋白与肌动蛋白细胞骨架的机械耦合更强的这种行为。最后，我们表明，生长锥内的Vangl 2的空间分布是选择性地影响由N-钙粘蛋白涂层基板。总之，我们的数据表明，Vangl 2作为轴突生长的负调节剂，通过调节N-钙粘蛋白和肌动蛋白细胞骨架之间的分子离合器的强度。
Dynamic mechanical interactions between adhesion complexes and the cytoskeleton are essential for axon outgrowth and guidance. Whether planar cell polarity (PCP) proteins, which regulate cytoskeleton dynamics and appear necessary for some axon guidance, also mediate interactions with membrane adhesion is still unclear. Here we show that Vangl2 controls growth cone velocity by regulating the internal retrograde actin flow in an N-cadherin-dependent fashion. Single molecule tracking experiments show that the loss of Vangl2 decreased fast-diffusing N-cadherin membrane molecules and increased confined N-cadherin trajectories. Using optically manipulated N-cadherin-coated microspheres, we correlated this behavior to a stronger mechanical coupling of N-cadherin with the actin cytoskeleton. Lastly, we show that the spatial distribution of Vangl2 within the growth cone is selectively affected by an N-cadherin-coated substrate. Altogether, our data show that Vangl2 acts as a negative regulator of axonal outgrowth by regulating the strength of the molecular clutch between N-cadherin and the actin cytoskeleton.