Back to Search
Start Over
Cyclic AMP–dependent protein kinase phosphorylation facilitates GABAB receptor–effector coupling
- Source :
- Nature Neuroscience. 5:415-424
- Publication Year :
- 2002
- Publisher :
- Springer Science and Business Media LLC, 2002.
-
Abstract
- GABA (gamma-aminobutyric acid)(B) receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. Here we show that the functional coupling of GABA(B)R1/GABA(B)R2 receptors to inwardly rectifying K(+) channels rapidly desensitizes. This effect is alleviated after direct phosphorylation of a single serine residue (Ser892) in the cytoplasmic tail of GABA(B)R2 by cyclic AMP (cAMP)-dependent protein kinase (PKA). Basal phosphorylation of this residue is evident in rat brain membranes and in cultured neurons. Phosphorylation of Ser892 is modulated positively by pathways that elevate cAMP concentration, such as those involving forskolin and beta-adrenergic receptors. GABA(B) receptor agonists reduce receptor phosphorylation, which is consistent with PKA functioning in the control of GABA(B)-activated currents. Mechanistically, phosphorylation of Ser892 specifically enhances the membrane stability of GABA(B) receptors. We conclude that signaling pathways that activate PKA may have profound effects on GABA(B) receptor-mediated synaptic inhibition. These results also challenge the accepted view that phosphorylation is a universal negative modulator of G protein-coupled receptors.
- Subjects :
- Patch-Clamp Techniques
Potassium Channels
CHO Cells
GABAB receptor
Biology
Serine
chemistry.chemical_compound
Cricetinae
Cyclic AMP
Animals
Humans
Protein Isoforms
Enzyme Inhibitors
Phosphorylation
Protein kinase A
Receptor
GABA Agonists
Cells, Cultured
Brain Chemistry
Neurons
Forskolin
Effector
General Neuroscience
Cell Membrane
Brain
Phosphoproteins
Cyclic AMP-Dependent Protein Kinases
Recombinant Proteins
Rats
Cell biology
Receptors, GABA-B
nervous system
chemistry
Biochemistry
GABA-B Receptor Agonists
COS Cells
Signal transduction
Neuroscience
Signal Transduction
Subjects
Details
- ISSN :
- 15461726 and 10976256
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Nature Neuroscience
- Accession number :
- edsair.doi.dedup.....176dc3838da2052dec8361bf246fcbd8