Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2004

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

Résumé

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.
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Dates et versions

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

Identifiants

Citer

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⟩
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