A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors.
J Biol Chem
; 300(2): 105649, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38237683
ABSTRACT
Class A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors, moonlight as constitutively active phospholipid scramblases. The plasma membrane of metazoan cells is replete with GPCRs yet has a strong resting trans-bilayer phospholipid asymmetry, with the signaling lipid phosphatidylserine confined to the cytoplasmic leaflet. To account for the persistence of this lipid asymmetry in the presence of GPCR scramblases, we hypothesized that GPCR-mediated lipid scrambling is regulated by cholesterol, a major constituent of the plasma membrane. We now present a technique whereby synthetic vesicles reconstituted with GPCRs can be supplemented with cholesterol to a level similar to that of the plasma membrane and show that the scramblase activity of two prototypical GPCRs, opsin and the ß1-adrenergic receptor, is impaired upon cholesterol loading. Our data suggest that cholesterol acts as a switch, inhibiting scrambling above a receptor-specific threshold concentration to disable GPCR scramblases at the plasma membrane.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fosfolípidos
/
Receptores Acoplados a Proteínas G
Idioma:
En
Revista:
J Biol Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos