Spatial-temporal patterning of metabotropic glutamate receptor-mediated inositol 1,4,5-triphosphate, calcium, and protein kinase C oscillations - Protein kinase C-dependent receptor phosphorylation is not required

John P. Robarts Research Institute, P. O. Box 5015, 100 Perth Drive, London, Ontario N6A 5K8, Canada.
Journal of Biological Chemistry (Impact Factor: 4.57). 10/2001; 276(38):35900-8. DOI: 10.1074/jbc.M103847200
Source: PubMed


The metabotropic glutamate receptors (mGluR), mGluR1a and mGluR5a, are G protein-coupled receptors that couple via Gq to the hydrolysis of phosphoinositides, the release of Ca2+ from intracellular stores, and the activation of protein kinase C (PKC). We show here that mGluR1/5 activation results in
oscillatory G protein coupling to phospholipase C thereby stimulating oscillations in both inositol 1,4,5-triphosphate formation
and intracellular Ca2+ concentrations. The mGluR1/5-stimulated Ca2+ oscillations are translated into the synchronized repetitive redistribution of PKCβII between the cytosol and plasma membrane.
The frequency at which mGluR1a and mGluR5a subtypes stimulate inositol 1,4,5-triphosphate, Ca2+, and PKCβII oscillations is regulated by the charge of a single amino acid residue localized within their G protein-coupling
domains. However, oscillatory mGluR signaling does not involve the repetitive feedback phosphorylation and desensitization
of mGluR activity, since mutation of the putative PKC consensus sites within the first and second intracellular loops as well
as the carboxyl-terminal tail does not prevent mGluR1a-stimulated PKCβII oscillations. Furthermore, oscillations in Ca2+ continued in the presence of PKC inhibitors, which blocked PKCβII redistribution from the plasma membrane back into the cytosol.
We conclude that oscillatory mGluR signaling represents an intrinsic receptor/G protein coupling property that does not involve
PKC feedback phosphorylation.

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