title: Post-transcriptional regulation of GABAB receptor and GIRK1 channels by Nogo receptor 1.
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.
authors.affiliation: Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System-Neurology and GRECC, 5027 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
authors.forename: Rachana
authors.initials: R
authors.lastname: Murthy
authors.forename: Jeeyong
authors.initials: J
authors.lastname: Kim
authors.forename: Xiankui
authors.initials: X
authors.lastname: Sun
authors.forename: Roman J
authors.initials: RJ
authors.lastname: Giger
authors.forename: David J
authors.initials: DJ
authors.lastname: Fink
authors.forename: Marina
authors.initials: M
authors.lastname: Mata
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics* / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000378:metabolism*; D000070816:Nogo Receptor 1; D021122:Protein Subunits / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000235:genetics* / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D021122:Protein Subunits; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D018080:Receptors, GABA-B; C419790:Rtn4r protein, mouse; C486581:Rtn4r protein, rat; D020123:Sirolimus