G protein-coupled receptor kinases regulate metabotropic glutamate receptor 5 function and expression.
Metabotropic glutamate receptors (mGluR) serve important neuromodulatory roles at glutamatergic synapses to shape excitatory neurotransmission. Recent evidence indicates that the desensitization of mGluRs is an important determinant in regulating the functions of these receptors. The present results demonstrate that G protein-coupled receptor kinases (GRKs), which are known to regulate the desensitization of many G protein-coupled receptors, regulate both the expression and function of mGluR5 in a heterologous expression system. This regulatory event is limited to members of the GRK2 family since GRK4 family members do not elicit the same effects on mGluR5. Kinase activity is shown to be required for GRK-mediated regulation of mGluR5. Furthermore, the ability of GRK2 to regulate mGluR5 is dependent, at least in part, on the presence of threonine 840 in the carboxyl terminus of mGluR5. These studies identify novel roles for GRKs in regulating mGluR5 that may serve to further shape the function of these receptors in neurotransmission.
Sorensen
Scott D
SD
Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA. ssorens@emory.edu
Conn
P Jeffrey
PJ
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D051552:beta-Adrenergic Receptor Kinases
C578935:GRM5 protein, human; C578937:Grm5 protein, rat; D020033:Protein Isoforms; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases