GABAB receptor cell-surface export is controlled by an endoplasmic reticulum gatekeeper.

Détails

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_1310325DA384
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
GABAB receptor cell-surface export is controlled by an endoplasmic reticulum gatekeeper.
Périodique
Molecular psychiatry
Auteur⸱e⸱s
Doly S., Shirvani H., Gäta G., Meye F.J., Emerit M.B., Enslen H., Achour L., Pardo-Lopez L., Yang S.K., Armand V., Gardette R., Giros B., Gassmann M., Bettler B., Mameli M., Darmon M., Marullo S.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Statut éditorial
Publié
Date de publication
04/2016
Peer-reviewed
Oui
Volume
21
Numéro
4
Pages
480-490
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Endoplasmic reticulum (ER) release and cell-surface export of many G protein-coupled receptors (GPCRs) are tightly regulated. For gamma-aminobutyric acid (GABA)B receptors of GABA, the major mammalian inhibitory neurotransmitter, the ligand-binding GB1 subunit is maintained in the ER by unknown mechanisms in the absence of hetero-dimerization with the GB2 subunit. We report that GB1 retention is regulated by a specific gatekeeper, PRAF2. This ER resident transmembrane protein binds to GB1, preventing its progression in the biosynthetic pathway. GB1 release occurs upon competitive displacement from PRAF2 by GB2. PRAF2 concentration, relative to that of GB1 and GB2, tightly controls cell-surface receptor density and controls GABAB function in neurons. Experimental perturbation of PRAF2 levels in vivo caused marked hyperactivity disorders in mice. These data reveal an unanticipated major impact of specific ER gatekeepers on GPCR function and identify PRAF2 as a new molecular target with therapeutic potential for psychiatric and neurological diseases involving GABAB function.

Mots-clé
Amino Acid Sequence, Animals, Carrier Proteins/metabolism, Cell Line, Cell Membrane/metabolism, Endoplasmic Reticulum/metabolism, HEK293 Cells, Humans, Membrane Proteins/metabolism, Mice, Mice, Knockout, Protein Multimerization, Protein Subunits, Receptors, GABA-B/metabolism, gamma-Aminobutyric Acid/metabolism
Pubmed
Création de la notice
24/03/2017 14:07
Dernière modification de la notice
20/08/2019 12:41
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