Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors. - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2004

Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors.

(1) , (1) , (1) , (1) , (1) , (2) , (3) , (1) , (1)
1
2
3

Abstract

Although agonists bind directly in the heptahelical domain (HD) of most class-I rhodopsin-like G protein coupled receptors (GPCRs), class-III agonists bind in the extracellular domain of their receptors. Indeed, the latter possess a large extracellular domain composed of a cysteine-rich domain and a Venus flytrap module. Both the low sequence homology and the structural organization of class-III GPCRs raised the question of whether or not the HD of these receptors functions the same way as rhodopsin-like GPCRs. Here, we show that the HD of metabotropic glutamate receptor 5 (mGlu(5)) displays the same agonist-independent constitutive activity as the wild-type receptor. Moreover, we show that the noncompetitive antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine hydrochloride] and the positive allosteric modulator DFB (3,3'-difluorobenzaldazine) act as inverse agonist and full agonist, respectively, on the mGlu(5) HD in the absence of the extracellular domain. This finding illustrates that, like rhodopsin-like receptors, the HD of mGluRs can constitutively couple to G proteins and be negatively and positively regulated by ligands. These data show that the HD of mGluRs behave like any other class-I GPCRs in terms of G protein coupling and regulation by various types of ligands.
Fichier principal
Vignette du fichier
MS03-4699-short.pdf (388 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

inserm-00319003 , version 1 (05-09-2008)

Identifiers

Cite

Cyril Goudet, Florence Gaven, Julie Kniazeff, Claire Vol, Jianfeng Liu, et al.. Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors.. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101 (1), pp.378-83. ⟨10.1073/pnas.0304699101⟩. ⟨inserm-00319003⟩
161 View
339 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More