Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, EpiSciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Evidence for a single heptahelical domain being turned on upon activation of a dimeric GPCR.

Abstract : G-protein-coupled receptors (GPCRs) have been shown to form dimers, but the relevance of this phenomenon in G-protein activation is not known. Among the large GPCR family, metabotropic glutamate (mGlu) receptors are constitutive dimers. Here we examined whether both heptahelical domains (HDs) are turned on upon full receptor activation. To that aim, we measured G-protein coupling efficacy of dimeric mGlu receptors in which one subunit bears specific mutations. We show that a mutation in the third intracellular loop (i3 loop) known to prevent G-protein activation in a single subunit decreases coupling efficacy. However, when a single HD is blocked in its inactive state using an inverse agonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), no decrease in receptor activity is observed. Interestingly, in a receptor dimer in which the subunit that binds MPEP is mutated in its i3 loop, MPEP enhances agonist-induced activity, reflecting a 'better' activation of the adjacent HD. These data are consistent with a model in which a single HD is turned on upon activation of such homodimeric receptors and raise important issues in deciphering the functional role of GPCR dimer formation for G-protein activation.
Complete list of metadata

Cited literature [55 references]  Display  Hide  Download
Contributor : Cyril Goudet Connect in order to contact the contributor
Submitted on : Friday, September 5, 2008 - 11:15:57 AM
Last modification on : Tuesday, July 5, 2022 - 8:52:57 AM
Long-term archiving on: : Monday, October 8, 2012 - 12:56:26 PM


Files produced by the author(s)




Veronika Hlavackova, Cyril Goudet, Julie Kniazeff, Alice Zikova, Damien Maurel, et al.. Evidence for a single heptahelical domain being turned on upon activation of a dimeric GPCR.. EMBO Journal, EMBO Press, 2005, 24 (3), pp.499-509. ⟨10.1038/sj.emboj.7600557⟩. ⟨inserm-00318934⟩



Record views


Files downloads