Unique Role of Dystroglycan in Peripheral Nerve Myelination, Nodal Structure, and Sodium Channel Stabilization

Neuron. 2003 Jun 5;38(5):747-58. doi: 10.1016/s0896-6273(03)00301-5.

Abstract

Dystroglycan is a central component of the dystrophin-glycoprotein complex implicated in the pathogenesis of several neuromuscular diseases. Although dystroglycan is expressed by Schwann cells, its normal peripheral nerve functions are unknown. Here we show that selective deletion of Schwann cell dystroglycan results in slowed nerve conduction and nodal changes including reduced sodium channel density and disorganized microvilli. Additional features of mutant mice include deficits in rotorod performance, aberrant pain responses, and abnormal myelin sheath folding. These data indicate that dystroglycan is crucial for both myelination and nodal architecture. Dystroglycan may be required for the normal maintenance of voltage-gated sodium channels at nodes of Ranvier, possibly by mediating trans interactions between Schwann cell microvilli and the nodal axolemma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Cell Membrane / ultrastructure
  • Cells, Cultured
  • Cytoskeletal Proteins / deficiency*
  • Cytoskeletal Proteins / genetics
  • Dystroglycans
  • Laminin / genetics
  • Laminin / metabolism
  • Macromolecular Substances
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Knockout
  • Movement Disorders / genetics
  • Movement Disorders / metabolism
  • Movement Disorders / physiopathology
  • Mutation / genetics
  • Myelin Sheath / metabolism*
  • Myelin Sheath / pathology
  • Myelin Sheath / ultrastructure
  • Neural Conduction / genetics
  • Peripheral Nerves / growth & development*
  • Peripheral Nerves / pathology
  • Peripheral Nerves / ultrastructure
  • Protein Binding / genetics
  • Ranvier's Nodes / metabolism*
  • Ranvier's Nodes / pathology
  • Ranvier's Nodes / ultrastructure
  • Schwann Cells / metabolism*
  • Schwann Cells / ultrastructure
  • Sodium Channels / metabolism*
  • Wallerian Degeneration / genetics
  • Wallerian Degeneration / metabolism
  • Wallerian Degeneration / physiopathology

Substances

  • Cytoskeletal Proteins
  • Laminin
  • Macromolecular Substances
  • Membrane Glycoproteins
  • Sodium Channels
  • Dystroglycans