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 receptors that mediate feedback inhibition of glutamate release via a Ca(2+)/calmodulin (CaM)-dependent mechanism. In vitro phosphorylation of mGluR7A by protein kinase C (PKC) prevents its interaction with Ca(2+)/CaM. In addition, activation of PKC leads to an inhibition of mGluR signaling. Here, we demonstrate that disrupting CaM binding to mGluR7A by PKC in vitro is due to phosphorylation of a highly conserved serine residue, S862. We propose charge neutralization of the CaM binding consensus sequence resulting from phosphorylation to constitute a general mechanism for the regulation of presynaptic mGluR signaling.
Airas
J M
JM
Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstrasse 46, 60528, Frankfurt, Germany.
Betz
H
H
El Far
O
O
D000595:Amino Acid Sequence; D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism*; D017124:Conserved Sequence; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism*
D002147:Calmodulin; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; C102718:metabotropic glutamate receptor 3; D012694:Serine; D011493:Protein Kinase C