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

Development. 2020 Feb 4;147(3):dev174540. doi: 10.1242/dev.174540.

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 RalA GTPase as a key player in axon ensheathment in Drosophila larval peripheral nerves. We demonstrate through genetic analysis that RalA action through the exocyst complex is required in wrapping glial cells to regulate their growth and development. We suggest that the RalA-exocyst pathway controls the targeting of secretory vesicles for membrane growth or for the secretion of a wrapping glia-derived 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 that is crucial for normal neuronal function.

Keywords: Axonal ensheathment; Drosophila; Exocyst; RalA GTPase; Wrapping glia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axon Fasciculation / genetics
  • Axons / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Larva / metabolism
  • Locomotion / genetics
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Mutation
  • Myelin Sheath / metabolism*
  • Neuroglia / metabolism
  • Peripheral Nerves / metabolism*
  • RNA Interference
  • Vesicular Transport Proteins / metabolism*

Substances

  • Drosophila Proteins
  • Vesicular Transport Proteins
  • Monomeric GTP-Binding Proteins
  • RalA protein, Drosophila