Physiological role of protein synthesis in nerve growth cone

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The aim of this study is to clarity the physiological roles of local protein synthesis in change of motility and morphology of nerve growth cone in response to extracellular stimuli. In 2002, we examined the roles of local protein synthesis in neurite outgrowth induced by nerve growth factor using chick dorsal root ganglion cells cultured on laminin. We first investigated the expression and distribution patterns of calcium-regulated protein translational factor, eukaryotic elongation factor-2 (eEF2). We found that phosphorylated eEF2 was distributed in the cell body and the growth cones, but the expression level was low. The cells exposed to high KCl stimulus showed growth cone collapse and inhibition of neurite outgrowth, and the expression level of phosphorylated eEF2 was significantly increased with intracellular calcium transient induced by high KCl stimulus, suggesting that eEF2 within growth cones was phosphorylated in a calcium-dependent manner and was involved in the signal cascade regulating neurite outgrowth. In 2003, we examined the roles of local protein synthesis in growth cone collapse induced by semaphoring 3A (Sema3A). Sema3A induced phosphorylation of eIF4E and blockade of protein synthesis with anisomycin inhibited the growth cone collapse. The cells to expose to Fyn kinase inhibitor, lavemdustin-A showed decrease of eIF4E phosphorylation of eIF4E induced by Sema3A. Since Sema3A signaling is considered to be independent of calcium signaling, it is suggested that neurite outgrowth and growth cone collapse mediated by local protein synthesis are independently regulated.