Semaphorin3A facilitates axonal transport through a local calcium signaling and tetrodotoxin-sensitive voltage-gated sodium channels

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 Ca2+ 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.

► Sema3A facilitates axonal transport via L-type VGCC, RyR and TTX-sensitive VGSCs.
► Sema3A evokes local Ca2+ elevation in growth cone.
► Sema3A activates RyR in growth cone as well as cell body.
► TTX suppressed Sema3A-induced RyR activation in cell body but not in growth cone.