A multi PDZ-domain protein Pdzd2 contributes to functional expression of sensory neuron-specific sodium channel Na(V)1.8

Mol Cell Neurosci. 2009 Nov;42(3):219-25. doi: 10.1016/j.mcn.2009.07.003. Epub 2009 Jul 14.

Abstract

The voltage-gated sodium channel Na(V)1.8 is expressed exclusively in nociceptive sensory neurons and plays an important role in pain pathways. Na(V)1.8 cannot be functionally expressed in non-neuronal cells even in the presence of beta-subunits. We have previously identified Pdzd2, a multi PDZ-domain protein, as a potential interactor for Na(V)1.8. Here we report that Pdzd2 binds directly to the intracellular loops of Na(V)1.8 and Na(V)1.7. The endogenous Na(V)1.8 current in sensory neurons is inhibited by antisense- and siRNA-mediated downregulation of Pdzd2. However, no marked change in pain behaviours is observed in Pdzd2-decificent mice. This may be due to compensatory upregulation of p11, another regulatory factor for Na(V)1.8, in dorsal root ganglia of Pdzd2-deficient mice. These findings reveal that Pdzd2 and p11 play collaborative roles in regulation of Na(V)1.8 expression in sensory neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Adhesion Molecules
  • Cells, Cultured
  • Ganglia, Spinal / cytology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • NAV1.7 Voltage-Gated Sodium Channel
  • NAV1.8 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • PDZ Domains*
  • Pain / metabolism
  • Pain Measurement
  • Protein Binding
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / metabolism*
  • Sequence Alignment
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • NAV1.7 Voltage-Gated Sodium Channel
  • NAV1.8 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • PDZD2 protein, rat
  • Pdzd2 protein, mouse
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Scn10a protein, mouse
  • Scn10a protein, rat
  • Scn9a protein, rat
  • Sodium Channels