Drp2 and periaxin form Cajal bands with dystroglycan but have distinct roles in Schwann cell growth

J Neurosci. 2012 Jul 4;32(27):9419-28. doi: 10.1523/JNEUROSCI.1220-12.2012.

Abstract

Cajal bands are cytoplasmic channels flanked by appositions where the abaxonal surface of Schwann cell myelin apposes and adheres to the overlying plasma membrane. These appositions contain a dystroglycan complex that includes periaxin and dystrophin-related protein 2 (Drp2). Loss of periaxin disrupts appositions and Cajal bands in Schwann cells and causes a severe demyelinating neuropathy in mouse and human. Here, we investigated the role of mouse Drp2 in apposition assembly and Cajal band function and compared it with periaxin. We show that periaxin and Drp2 are not only both required to form appositions, but they must also interact. Periaxin-Drp2 interaction is also required for Drp2 phosphorylation, but phosphorylation is not required for the assembly of appositions. Drp2 loss causes corresponding increases in Dystrophin family members, utrophin and dystrophin Dp116, although dystroglycan remains unchanged. We also show that all dystroglycan complexes in Schwann cells use the uncleaved form of β-dystroglycan. Drp2-null Schwann cells have disrupted appositions and Cajal bands, and they undergo focal hypermyelination and concomitant demyelination. Nevertheless, they do not have the short internodal lengths and associated reduced nerve conduction velocity seen in the absence of periaxin, showing that periaxin regulates Schwann cell elongation independent of its role in the dystroglycan complex. We conclude that the primary role of the dystroglycan complex in appositions is to stabilize and limit the radial growth of myelin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dystroglycans / physiology*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Nerve Crush / methods
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Schwann Cells / cytology
  • Schwann Cells / physiology*
  • Sciatic Neuropathy / metabolism
  • Sciatic Neuropathy / pathology
  • Sciatic Neuropathy / physiopathology

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • collapsin response mediator protein-2
  • periaxin
  • Dystroglycans