Peripheral axonal ensheathment is regulated by Ral GTPase and the exocyst complex

Abstract Axon ensheathment is fundamental for fast impulse conduction and the normal physiological functioning of the nervous system. Defects in axonal insulation lead to debilitating conditions, but despite its importance, the molecular players responsible are poorly defined. Here, we identify Ral GTPase as a key player in axon ensheathment in Drosophila larval peripheral nerves. We demonstrate through genetic analysis that Ral action through the exocyst complex is sufficient and necessary in wrapping glial cells to regulate their growth and development. We suggest that the Ral-exocyst pathway controls the targeting of secretory vesicles for membrane growth or for the secretion of a wrapping glia-specific factor that itself regulates growth. In summary, our findings provide a new molecular understanding of the process by which axons are ensheathed in vivo , a process critical for normal neuronal function.