Abstract
Regulator of G Protein Signaling 6 (RGS6) ensures coordination of motor movement by modulating GABA B Receptor (GABA B R) signaling
The FASEB journal, Vol.26(S1)
04/2012
DOI: 10.1096/fasebj.26.1_supplement.972.8
Abstract
Abstract only Inhibitory interneurons located within the cerebellar cortex release GABA, which limits neuronal excitation in part through activation of metabatropic GABA B Rs. Here, we identify RGS6, a member of the R7 subfamily of RGS proteins, as a key modulator of GABA B R signaling in cerebellum. RGS6 −/− mice exhibit abnormal gait and ataxia characterized by impaired rotarod performance that can be partially rescued by administration of a GABA B R antagonist. In addition, RGS6 −/− mice treated with baclofen, a GABA B R agonist, show exaggerated motor coordination deficits on the rotarod compared to their wild type counterparts. Stimulation of GABA B Rs triggers a number of signaling events downstream of G protein activation including Gβγ subunit activation of G protein‐coupled inwardly rectifying potassium (GIRK) channels. Indeed, RGS6 is enriched in the granule cell layer of the cerebellum along with neuronal GIRK channel subunits 1 and 2 where RGS6 forms a complex with known binding partners Gβ 5 and R7‐binding protein (R7BP), which stabilize and promote membrane association of R7 family members, respectively. Cerebellar granule neurons isolated from RGS6 −/− mice showed a significant delay in the deactivation kinetics of baclofen‐induced GIRK currents. These results establish RGS6 as a key modulator of GABA B R signaling, providing the first demonstration of an essential role for RGS proteins in cerebellar function.
Details
- Title: Subtitle
- Regulator of G Protein Signaling 6 (RGS6) ensures coordination of motor movement by modulating GABA B Receptor (GABA B R) signaling
- Creators
- Adele Stewart - University of IowaBiswanath Maity - University of IowaJianqi Yang - University of IowaLipin Loo - University of IowaAndrew J Shepherd - University of IowaDurga P Mohapatra - University of IowaRory A Fisher - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.26(S1)
- DOI
- 10.1096/fasebj.26.1_supplement.972.8
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Language
- English
- Date published
- 04/2012
- Academic Unit
- Neuroscience and Pharmacology; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984618498702771
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