Isoform-specific and pan-channel partners regulate trafficking and plasma membrane stability; and alter sodium channel gating properties

Neurosci Lett. 2010 Dec 10;486(2):84-91. doi: 10.1016/j.neulet.2010.08.077. Epub 2010 Sep 17.

Abstract

Voltage-gated sodium channels are cell membrane glycoproteins responsible for action potential generation and propagation in excitable cells. These large polypeptides which are comprised of 24 transmembrane segments organized into four domains require cellular factors to regulate channel maturation and sorting to different cellular compartments, anchoring the channels at plasma membrane, and modulating gating properties of these channels as effector molecules in the signal transduction pathway. Mutations of sodium channels or their cytosolic partners produce similar pathologies, providing a compelling evidence for the biological significance of channel complexes that form during channel biogenesis and following sorting to different cellular compartments and anchoring at plasma membrane. Genetic, biochemical and bioinformatic approaches have been utilized to identify sodium channel partners. Here we review the important functional role of pan-sodium channel and isoform-specific partners in regulating sodium current density and gating properties.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / physiology
  • Animals
  • Calmodulin / genetics
  • Calmodulin / physiology
  • Cell Membrane / metabolism
  • Contactins / genetics
  • Contactins / physiology
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / physiology
  • Humans
  • Ion Channel Gating
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / physiology
  • Mutation
  • Protein Interaction Mapping
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Stability
  • Protein Transport
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / physiology

Substances

  • Adaptor Proteins, Vesicular Transport
  • Calmodulin
  • Contactins
  • Protein Isoforms
  • Sodium Channels
  • Fibroblast Growth Factors
  • Ubiquitin-Protein Ligases
  • Mitogen-Activated Protein Kinases