Cloning and characterization of a bifunctional metabotropic receptor activated by both extracellular calcium and glutamate.
A cDNA from salmon brain which induces a consistent activation of Ca2+ dependent Cl- (Ca(2+)-Cl-) current in Xenopus oocytes in the saline solution was isolated by an expression cloning method. The primary structure showed a high homology with the metabotropic glutamate receptors (mGluR), and a limited homology with the Ca2+/polyvalent cation receptors (CaR). The encoded protein was functionally characterized for the sensitivity to extracellular Ca2+ (Cao2+), and the consistent activation of Ca(2+)-Cl- current was determined to be due to Ca2+ contained in the saline solution. It was also confirmed that the encoded protein has a function to sense glutamate. An increase in inositol 1,4,5-triphosphate turnover was observed when either Ca2+ or glutamate was applied. Thus, the encoded protein was identified as a bifunctional metabotropic receptor for both Ca2+ and glutamate. In addition, rat mGluR1 alpha was also shown to be activated by Cao2+. This is the first report of a G-protein coupled receptor which is activated by two totally different physiological agonists.
Kubokawa
K
K
Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Japan.
Miyashita
T
T
Nagasawa
H
H
Kubo
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D003001:Cloning, Molecular; D004594:Electrophysiology; D029941:Fish Proteins; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D012474:Salmon; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
D015220:Calcium Channels; D018118:Chloride Channels; D029941:Fish Proteins; D018094:Receptors, Metabotropic Glutamate; C101103:SBimR protein, Oncorhynchus masou; D018698:Glutamic Acid; D015544:Inositol 1,4,5-Trisphosphate; D019204:GTP-Binding Proteins; D002118:Calcium