Abstract
Metabotropic glutamate receptor 1 (mGluR1) is crucial for some forms of synaptic plasticity. A wild type mGluR1 (mGluR1α) is known to functionally couple to different types of G proteins, such as Gq, Gs and Gi/o, whereas a short form splice variant, mGluR1β, has been reported not to functionally couple with Gs. We have confirmed the regulation of dual signals via mGluR1α, Gs and Gq in CHO cells, by C-terminal tail and recently have demonstrated that interaction with a cytoskeletal protein, 4.1G, inhibited the Gs coupling but not Gq. The mGluR1β is reportedly known to exhibit different dual signals, Gi/o and Gq, in BHK cells. In this study, we observed that in HEK cells mGluR1α functionally couples with Gi/o and Gq, which were monitored by a combination of FRET based-cAMP indicator and Ca2+ indicator, as a decrease in intracellular cAMP concentration ([cAMP]i) and an increase in intracellular Ca2+ concentration ([Ca2+]i), respectively. In addition, activation of mGluR1α evoked an inward current through co-transfected G protein-gated inwardly rectifying K+ (GIRK) channels, indicting the direct interaction of mGluR1α with Gi/o. The mGluR1β could not decrease the [cAMP]i but could increase the [Ca2+]i, which indicates that the dual signals of mGluR1 in HEK cells, activation of Gi/o and Gq, were also regulated by C-terminal tail. [J Physiol Sci. 2007;57 Suppl:S86]
