Department of Molecular Pharmacology and Neurobiology, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan.
Biochem Biophys Res Commun. 2012 Jun 1;422(2):333-8. doi: 10.1016/j.bbrc.2012.05.003. Epub 2012 May 7.
Semaphorin3A (Sema3A), a secreted factor that navigates axons and dendrites of developing neurons, facilitates axonal transport. However, little is known about the mechanism underlying Sema3A-induced facilitation and its functional implications. Here we show that Sema3A induces facilitation of axonal transport via local calcium signaling in growth cone. The facilitation of axonal transport was blocked by inhibitors of voltage-gated sodium channels (tetrodotoxin, TTX), L-type voltage-gated calcium channel, and ryanodine receptor (RyR). Sema3A evoked intracellular Ca(2+) elevation in growth cone by local application of Sema3A to growth cone. Sema3A also activated RyR in growth cone as well as cell body. Notably, TTX suppressed Sema3A-induced RyR activation in cell body but not in growth cone. Our results identify a novel mechanism of Sema3A-induced axonal transport, and further suggest that Sema3A-induced local calcium signaling in growth cone is propagated to cell body in a TTX-sensitive manner.
神经递质蛋白 3A（Sema3A）是一种能够引导神经元轴突和树突发育的分泌因子，促进轴突运输。然而，对于 Sema3A 诱导促进作用的机制及其功能意义知之甚少。在这里，我们发现 Sema3A 通过生长锥内的局部钙信号诱导轴突运输的促进作用。轴突运输的促进作用被电压门控钠离子通道（河豚毒素，TTX）、L 型电压门控钙通道和兰尼碱受体（RyR）抑制剂阻断。通过局部应用 Sema3A 到生长锥，Sema3A 引起生长锥内细胞内 Ca(2+)的升高。Sema3A 还能在生长锥和细胞体中激活 RyR。值得注意的是，TTX 抑制了 Sema3A 在细胞体中引起的 RyR 激活，但在生长锥中没有抑制。我们的研究结果确定了 Sema3A 诱导的轴突运输的一种新机制，并进一步表明 Sema3A 在生长锥中诱导的局部钙信号以 TTX 敏感的方式传递到细胞体。
