Functional regulation of metabotropic glutamate receptor type 1c: a role for phosphorylation in the desensitization of the receptor

The phosphorylation and desensitization of metabotropic glutamate receptor type lc in response to agonist and phorbol esters has been studied. Specifi c immunoprecipitation of mGluR1c from cells treated with agonist or PMA sho wed a time-dependent increase in the phosphorylation of a membrane protein with the same molecular weight as the dimeric form of the receptor, Measure ments of inositol phosphate production showed a rapid functional desensitiz ation of about 90% after agonist treatment, whereas treatment with PMA caus ed only a 30% loss in the same time, The extent of receptor phosphorylation following the different treatments paralleled the desensitization of the r eceptor, These results strongly suggest that phosphorylation of the dimeric form of mGIuR1c, as a functionally active form, may play a role in its rap id desensitization. (C) 1999 Federation of European Biochemical Societies.