Post-transcriptional regulation of GABAB receptor and GIRK1 channels by Nogo receptor 1

Mol Brain. 2013 Jul 6;6:30. doi: 10.1186/1756-6606-6-30.

Abstract

Background: Type B GABA receptors (GABA Rs) play a critical role in synaptic transmission. We carried out studies to determine whether neuronal cell surface expression of GABAB-Rs might be regulated by the Nogo receptor 1 (NgR1).

Results: siRNA knock-down of NgR1 resulted in a selective increase of GABAB R1 and GABAB R2 protein without altering the expression of GABAA receptor or GAD65. The increase in GABAB receptor subunits was unaccompanied by a change in mRNA, but inhibition of mTOR by rapamycin blocked the increase in GABAB protein. NgR1 siRNA also caused an increase in G protein coupled inwardly rectifying potassium channel (GIRK1). The increase in GABAB receptor and GIRK1 channel proteins was in the plasma membrane, determined by cell surface biotinylation. In NgR1 knockout mice, the amount of GABAB R2 and GIRK1 in hippocampus-derived synaptosomes was increased.

Conclusions: Together these findings suggest that NgR1 mediated modulation of synaptic transmission may be accomplished, at least in part, through modulation of G protein coupled receptors and channels.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics*
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation* / drug effects
  • Mice
  • Mice, Knockout
  • Myelin Proteins / metabolism*
  • Nogo Receptor 1
  • Protein Subunits / metabolism
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / metabolism*
  • Receptors, GABA-B / genetics*
  • Receptors, GABA-B / metabolism
  • Sirolimus / pharmacology
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Transcription, Genetic* / drug effects

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GPI-Linked Proteins
  • Myelin Proteins
  • Nogo Receptor 1
  • Protein Subunits
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Receptors, GABA-B
  • Rtn4r protein, mouse
  • Rtn4r protein, rat
  • Sirolimus