title: The intra-molecular activation mechanisms of the dimeric metabotropic glutamate receptor 1 differ depending on the type of G proteins.
abstract: Metabotropic glutamate receptor 1 (mGlu1) functions as a homodimer and activates not only the Gq but also the Gi/o and Gs pathways. Because of the dimeric configuration, different pathways could be activated either through the glutamate-bound subunit (cis-activation) and/or the other one (trans-activation). We here examined whether the intra-molecular activation mechanisms in the mGlu1 differ depending on the type of coupling G proteins, using various combinations of mGlu1 constructs that lack glutamate binding and/or G-protein coupling. The cis- or trans-activation alone was confirmed to trigger the Gq-coupled intracellular Ca(2+) transient. In contrast, the Gi/o-coupled G protein-dependent inward rectifying potassium (GIRK) channels were not activated either through the cis- or trans-activation alone. When one subunit of dimeric mGlu1 lacked the G-protein coupling, a significant decrease in the glutamate-induced GIRK current density was also observed. As the G protein-coupling-deficient subunit did not decrease the cell surface expression of mGlu1 and the Gq-coupled Ca(2+) transient, it was suggested that the coupling deficiency in one subunit of mGlu1 attenuates the Gi/o but not Gq coupling. In conclusion, multiple G-protein signaling was differentially activated by different intra-molecular activation mechanisms of the dimeric mGlu1.
authors.affiliation: Division of Biophysics and Neurobiology, Department of Molecular Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan. tateyama@nips.ac.jp
authors.forename: Michihiro
authors.initials: M
authors.lastname: Tateyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kubo
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D017354:Point Mutation / Q000235:genetics; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D019204:GTP-Binding Proteins