Abstract
The dimeric conformation of the G protein-coupled metabotropic glutamate receptor 1α (mGluR1α), which is a key determinant of the downstream signaling from the receptor, is crucial for some forms of synaptic plasticity. Moreover, crystallographic analysis has shown that glutamate and the antagonist (S)-MCPG respectively stabilize the active and resting states of the dimeric conformation of the extracellular domain. In the present study, we investigated the dimeric rearrangement of the cytoplasmic domain caused by ligand binding by analyzing the fluorescence resonance energy transfer (FRET) signal obtained from the plasma membrane, where ligands interact with the mGluR1α, using a total internal reflection field microscopy system. Intermolecular FRET efficiency was altered within 9 s after glutamate application, and the effect was concentration-dependent. (S)-MCPG inhibited the change by shifting the concentration-FRET efficiency relationship rightward. Alterations in FRET efficiency were also elicited by Ca2+ and Gd3+, which are known to activate mGluR1α. By contrast, intramolecular FRET efficiency was unaffected by glutamate. We therefore conclude that ligand-induced rearrangement of the extracellular dimeric conformation leads to intracellular dimeric rearrangement without altering the respective monomeric conformations. [Jpn J Physiol 54 Suppl:S140 (2004)]
