Regulatory role of C-terminus in the G-protein coupling of the metabotropic glutamate receptor 1.
The signaling property of metabotropic glutamate receptor 1alpha (mGlu1alpha) is different from that of short-form splice variants. This could be caused by the exposure of a cluster of positively charged amino acid residues, RRKK, in the proximal C-tail which is thought to be masked by the long C-tail of mGlu1alpha. We found that the RRKK residues, when exposed, attenuate Gq coupling and decrease the basal activity and the surface expression of mGlu1, in agreement with previous results. Moreover, these residues abolish the Gi/o coupling of mGlu1, but do not affect glutamate-induced dimeric rearrangement and protein kinase A-dependent modulation of mGlu1. These results suggest that the RRKK residues do not inhibit the conformational change upon glutamate binding and protein accessibility to the intracellular loops where G-protein coupling occurs, but rather act as an inhibitory domain against G-protein coupling in a different manner depending on the type of G protein.
Tateyama
Michihiro
M
Department of Molecular Physiology, Division of Biophysics and Neurobiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan. tateyama@nips.ac.jp
Kubo
Yoshihiro
Y
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D002867:Chromones / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008958:Models, Molecular; D009154:Mutation / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D037342:Pertussis Toxin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection / Q000379:methods
C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D002867:Chromones; D004791:Enzyme Inhibitors; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D005576:Colforsin; D018698:Glutamic Acid; D011189:Potassium Chloride; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium