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Metabotropic glutamate receptor 5‐regulated Elk‐1 phosphorylation and immediate early gene expression in striatal neurons
Author(s) -
Mao Limin,
Wang John Q.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01750.x
Subject(s) - metabotropic glutamate receptor 5 , medium spiny neuron , metabotropic glutamate receptor , ampa receptor , biology , metabotropic receptor , kainate receptor , phosphorylation , glutamate receptor , microbiology and biotechnology , immediate early gene , nmda receptor , striatum , neuroscience , gene expression , receptor , dopamine , biochemistry , gene
The Gαq protein‐coupled metabotropic glutamate receptor subtype‐5 (mGluR5) is densely expressed in medium spiny projection neurons of striatum. Emerging evidence suggests a significant role of mGluR5 in the addictive plasticity of striatal neurons that is likely derived from inducible cellular gene expression related to stimulation of mGluR5 and associative signaling proteins. In this study, we found that activation of mGluR5 with a selective agonist ( RS )‐2‐chloro‐5‐hydroxy‐phenylglycine (CHPG) induced a rapid and transient phosphorylation of a transcription regulator Elk‐1 in cultured striatal neurons from rat E19 embryos or neonatal day‐1 pups. The Elk‐1 phosphorylation was dose‐dependent and occurred in neurochemically identified GABAergic neurons, but not glia. A series of experiments further demonstrated that the CHPG‐stimulated Elk‐1 phosphorylation was mediated through selective activation of mGluR5‐regulated phospholipase C and associative second messenger system, i.e. 1,4,5,‐triphosphate‐sensitive Ca 2+ release. Moreover, the Elk‐1 phosphorylation was partially dependent on mGluR5‐mediated co‐activation of NMDA, but not kainate/AMPA receptors and L‐type voltage‐operated Ca 2+ channels. Using an immediate early gene c‐ fos as a report of inducible gene expression, we found that CHPG induced marked c‐ fos mRNA expression. The c‐ fos induction kinetically corresponded to the Elk‐1 phosphorylation and was attenuated by antisense oligonucleotides that selectively knocked down Elk‐1 proteins. These results indicate that glutamatergic tone on mGluR5 is positively coupled to Elk‐1 phosphorylation in striatal neurons via multiple signaling mechanisms involving Ca 2+ release and NMDA activation, and the mGluR5‐mediated Elk‐1 phosphorylation facilitates gene transcription.