Regulation of axonal outgrowth by mechano-sensor

人类的神经元可以长到1米以上，这是其特有的特征。这种延伸机制被称为“被动拉伸”。从胚胎阶段开始，被动的依赖拉伸的轴突生长开始。随着我们身体的生长，神经元细胞体和生长锥之间的距离逐渐增加，从而对轴突施加拉力。长期以来，人们一直没有确定哪些分子是它的机械传感器。我们之前报道过TRPV2是一个机械传感器通道，它以膜拉伸依赖的方式促进轴突的生长。这些结果表明，如果TRPV2能够检测到非常微弱的机械刺激，那么TRPV2可能是被动拉伸的重要组成部分。在这项研究中，我们通过Ca2+成像方法和全细胞膜片钳记录来检测TRPV2是否可以检测到这种非常微弱的机械刺激。我们还通过延时成像方法研究了弱机械刺激激活TRPV2是否会导致轴突生长增强。最后，我们发现TRPV2具有检测非常弱的机械刺激的潜力，并且TRPV2的激活促进了轴突的生长。综上所述，TRPV2是被动拉伸依赖性轴突生长的强有力候选分子。

It is specific characteristics that neurons can grow to the length of more than 1 m in humans. This mechanism of elongation has been called "passive stretching". From embryonic stages, the passive stretching-dependent axonal outgrowth begins. As our body grows, the distances between neuronal cell bodies and growth cones gradually increase, thereby exerting tensile forces on the axons. It has never been identified for a long time which molecules are the mechanosensors for it. We previously reported that TRPV2 was a mechanosensor channel which contributed axonal outgrowth in membrane stretch dependent manner. These results indicate that TRPV2 might be an important component for passive stretching, if TRPV2 can detect very weak mechanical stimulus. In this study, we examined whether TRPV2 can detect such very weak mechanical stimulus by a Ca2+-imaging method and a whole-cell patch clamp recording. We also examined whether the activation of TRPV2 by weak mechanical stimulus lead to the enhancement of axon outgrowth by a time-lapse imaging method. Finally, we identified that TRPV2 had a potential to detect very weak mechanical stimulus, and the activation of TRPV2 promoted axon outgrowth. Taken together, TRPV2 is a strong candidate molecule for passive stretch-dependent axonal outgrowth.