PHOSPHORYLATION AND CALMODULIN-BINDING OF THE METABOTROPIC GLUTAMATE-RECEPTOR SUBTYPE-5 (MGLUR5) ARE ANTAGONISTIC IN-VITRO

Metabotropic glutamate receptors, which are members of a G protein-cou pled receptor family, mediate the glutamate responses by coupling to t he intracellular signal transduction pathway, We herein report that ca lmodulin (CaM) interacts with the metabotropic glutamate receptor subt ype 5 (mGluR5) in a Ca2+-dependent manner in vitro, CaM is capable of binding on two distinct sites in the COOH-terminal intracellular regio n of the receptor with different affinities, The CaM binding domains a re separated by an alternatively spliced exon cassette present in one of the splicing isoforms of mGluR5, By using fusion proteins and synth etic peptides we showed that protein kinase C phosphorylates both CaM binding regions, This phosphorylation is inhibited by the binding of C aM to the receptor, and conversely the binding is inhibited by the pho sphorylation, These antagonisms of the CaM binding and phosphorylation thus suggest the possibility that they regulate the receptor response s in vivo.