RalGTPases contribute to Schwann cell repair after nerve injury via regulation of process formation

J Cell Biol. 2019 Jul 1;218(7):2370-2387. doi: 10.1083/jcb.201811002. Epub 2019 Jun 14.

Abstract

RalA and RalB are small GTPases that are involved in cell migration and membrane dynamics. We used transgenic mice in which one or both GTPases were genetically ablated to investigate the role of RalGTPases in the Schwann cell (SC) response to nerve injury and repair. RalGTPases were dispensable for SC function in the naive uninjured state. Ablation of both RalA and RalB (but not individually) in SCs resulted in impaired axon remyelination and target reinnervation following nerve injury, which resulted in slowed recovery of motor function. Ral GTPases were localized to the leading lamellipodia in SCs and were required for the formation and extension of both axial and radial processes of SCs. These effects were dependent on interaction with the exocyst complex and impacted on the rate of SC migration and myelination. Our results show that RalGTPases are required for efficient nerve repair by regulating SC process formation, migration, and myelination, therefore uncovering a novel role for these GTPases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Movement / genetics
  • Humans
  • Mice
  • Mice, Transgenic
  • Myelin Sheath / genetics
  • Nerve Regeneration / genetics*
  • Peripheral Nerve Injuries / genetics*
  • Peripheral Nerve Injuries / pathology
  • Schwann Cells / metabolism
  • Schwann Cells / pathology
  • Sciatic Nerve / injuries
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / pathology
  • ral GTP-Binding Proteins / genetics*

Substances

  • Rala protein, mouse
  • RalB protein, mouse
  • ral GTP-Binding Proteins