The mGluR proteins (metabotropic Glutamate Receptors) are members of the G protein-coupled receptor family and are functionally and pharmacologically distinct from the GluR proteins (ionotropic Glutamate Receptors). The eight currently known mGluR proteins are mediated by two G proteins with opposing regulation of adenylate cyclase pathways. The activities of mGluR1 and mGluR5 are mediated by a G protein that activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. The remainder of the eight sub-types of mGluR have an activity mediated by a G protein that inhibits adenylate cyclase activity. mGluR-5, which can interact with SIAH-1, RyR-1, RyR-2, ITPR1, Shank 1, Shank 3 and GRASP, acts as a receptor for glutamate. The PPXXf motif of mGluR-5 binds to HOM1, HOM2 and HOM3.
