The Succinate Receptor SUCNR1 Resides at the Endoplasmic Reticulum and Relocates to the Plasma Membrane in Hypoxic Conditions.
GPCR
N-glycosylation
SUCNR1/GPR91
angiogenesis
endoplasmic reticulum
succinate
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
13 07 2022
13 07 2022
Historique:
received:
17
05
2022
revised:
08
07
2022
accepted:
09
07
2022
entrez:
27
7
2022
pubmed:
28
7
2022
medline:
29
7
2022
Statut:
epublish
Résumé
The GPCR SUCNR1/GPR91 exerts proangiogenesis upon stimulation with the Krebs cycle metabolite succinate. GPCR signaling depends on the surrounding environment and intracellular localization through location bias. Here, we show by microscopy and by cell fractionation that in neurons, SUCNR1 resides at the endoplasmic reticulum (ER), while being fully functional, as shown by calcium release and the induction of the expression of the proangiogenic gene for VEGFA. ER localization was found to depend upon N-glycosylation, particularly at position N8; the nonglycosylated mutant receptor localizes at the plasma membrane shuttled by RAB11. This SUCNR1 glycosylation is physiologically regulated, so that during hypoxic conditions, SUCNR1 is deglycosylated and relocates to the plasma membrane. Downstream signal transduction of SUCNR1 was found to activate the prostaglandin synthesis pathway through direct interaction with COX-2 at the ER; pharmacologic antagonism of the PGE
Identifiants
pubmed: 35883628
pii: cells11142185
doi: 10.3390/cells11142185
pmc: PMC9321536
pii:
doi:
Substances chimiques
Receptors, G-Protein-Coupled
0
Succinates
0
Succinic Acid
AB6MNQ6J6L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CIHR
Pays : Canada
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