Group I Metabotropic Glutamate Receptor-mediated Gene Expression in Striatal Neurons

摘要

Group I mGluRs (mGluR1/5) are G-protein-coupled receptors and are abundantly expressed in most of medium spiny projection neurons in the striatum. Recent evidence demonstrates that group I mGluRs are among essential regulators for constitutive and inducible gene expression in host neurons. Upon activation, mGluR1/5 signals activate extracellular signal-regulated kinases (ERKs) which in turn phosphorylate transcription factors such as cAMP response element-binding protein (CREB) and Elk-1, and thereby facilitate immediate early gene and opioid peptide gene expression. The conventional mGluR1/5 signaling cascade (phosphoinositide hydrolysis and intracellular Ca2+ release) participates in linking mGluR1/5 to ERK. Additionally, the prominent mGluR1/5 adaptor protein Homer contributes to assemble an efficient signaling apparatus connecting mGluR1/5 to gene expression. The mGluR1/5 linkage to transcription also functions in dopamine-stimulated gene expression. Together, the mGluR1/5-mediated gene expression constitutes a transcription-dependent mechanism underlying molecular adaptations and plasticity related to the pathogenesis of various mental illnesses.