PKC phosphorylation of a conserved serine residue in the C-terminus of group III metabotropic glutamate receptors inhibits calmodulin binding

Group III metabotropic glutamate receptors (mGluRs) serve as presynaptic re ceptors that mediate feedback inhibition of glutamate release via a Ca2+/ca lmodulin (CaM)-dependent mechanism. In vitro phosphorylation of mGluR7A by protein kinase C (PKC) prevents its interaction with Ca2+/CaM. In addition, activation of PKC leads to an inhibition of mGluR signaling. Here, we demo nstrate that disrupting CaM binding to mGluR7A by PKC in vitro is due to ph osphorylation of a highly conserved serine residue, S862, We propose charge neutralization of the CaM binding consensus sequence resulting from phosph orylation to constitute a general mechanism for the regulation of presynapt ic mGluR signaling. (C) 2001 Federation of European Biochemical Societies, Published by Elsevier Science B,V, All rights reserved.