Sequential inter- and intrasubunit rearrangements during activation of dimeric metabotropic glutamate receptor 1

0381622 - ÚMG 2013 RIV US eng J - Journal Article
Hlaváčková, Veronika - Zabel, U. - Franková, Daniela - Batz, J. - Hoffmann, C. - Prezeau, L. - Pin, J. P. - Blahoš, Jaroslav - Lohse, M. J.
Sequential inter- and intrasubunit rearrangements during activation of dimeric metabotropic glutamate receptor 1.
Science Signaling. Roč. 5, č. 237 (2012), ra59. ISSN 1945-0877. E-ISSN 1937-9145
R&D Projects: GA ČR GA303/08/1591; GA MŠMT(CZ) LC06063; GA ČR GAP303/12/2408
Institutional research plan: CEZ:AV0Z50520514
Keywords : G-protein coupled receptor * metabotropic glutamate receptor 1 * class C GPCR
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 7.648, year: 2012

The metabotropic glutamate receptor 1 (mGluR1), a class C member of the heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor family, is a constitutive dimer that regulates excitatory neurotransmission. We investigated the role of homodimer formation in mGluR1 activation by examining activation-dependent inter-and intrasubunit conformational changes by fluorescence resonance energy transfer (FRET). We inserted yellow and cyan fluorescent proteins in the second intracellular loop and at the carboxyl terminus of mGluR1 to act as FRET sensors and expressed these proteins in human embryonic kidney 293 cells. Agonist-dependent activation of these mGluR1 chimeras rapidly increased the intersubunit FRET, suggesting rapid movement of the subunits relative to each other. After intersubunit movement, the intrasubunit FRET decreased, reflecting conformational changes within a subunit. Cotransfection of chimeric receptor subunits that were capable or incapable of G protein coupling revealed that only a single subunit assumes an active state in an mGluR1 receptor dimer.
Permanent Link: http://hdl.handle.net/11104/0216403