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Metabotropic glutamate receptor, mGluR5, signals from both the cell surface and from intracellular membranes
Author(s) -
O'Malley Karen,
Kumar Vikas,
Jong YuhJiin
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.205.2
Subject(s) - metabotropic glutamate receptor 5 , metabotropic glutamate receptor 1 , metabotropic glutamate receptor , metabotropic glutamate receptor 4 , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 3 , intracellular , chemistry , metabotropic glutamate receptor 2 , metabotropic receptor , glutamate receptor , membrane , microbiology and biotechnology , metabotropic glutamate receptor 8 , biophysics , receptor , biology , biochemistry
G‐protein coupled receptors transmit extracellular signals to the cytoplasm from their position on the cell surface. Some receptors including mGluR5 are also highly expressed on intracellular membranes where they serve unknown functions. Using a combination of permeable and impermeable agonists and antagonists as well as optical, cellular and genetic techniques, we tested whether activation of cell surface versus intracellular mGluR5 resulted in unique cellular responses. In striatal neurons expressing endogenous receptors, cell surface mGluR5 triggered rapid Ca 2+ transients resulting in JNK, CaMK, and CREB phosphorylation whereas stimulation of intracellular mGluR5 induced sustained Ca 2+ rises leading to the phosphorylation of ERK1/2 and Elk‐1 followed by the induction of synaptic plasticity genes like c‐fos, egr‐1, and Arc. These findings establish major molecular functions for intracellular mGluR5 in 1) the regulation of nuclear Ca 2+ , 2) transcriptional activation, and 3) upregulation of genes necessary for physiological processes like synaptic plasticity. Thus, agonistsand antagonists have differential effects on cell surface versus intracellular receptors depending upon their ability to cross cellular membranes or to be produced in situ. This work was supported by National Institutes of Health Grant MH69646 and the FRAXA and Simons Foundations.