A cholesterol switch controls phospholipid scrambling by G protein–coupled receptors Journal Article
| Authors: | Menon, I.; Sych, T.; Son, Y.; Morizumi, T.; Lee, J.; Ernst, O. P.; Khelashvili, G.; Sezgin, E.; Levitz, J.; Menon, A. K. |
| Article Title: | A cholesterol switch controls phospholipid scrambling by G protein–coupled receptors |
| 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 β1-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. © 2024 The Authors |
| Keywords: | signal transduction; controlled study; cell proliferation; proteins; fluorescence; cell membrane; cell membranes; cholesterol; g protein coupled receptor; liposome; bilayer membrane; phospholipids; phospholipid; cell signaling; single-particle; phosphatidylserine; plasma membrane; human; female; article; rhodopsin; opsin; g protein-coupled receptor; g protein coupled receptors; g protein-coupled receptor (gpcr); membrane transporter reconstitution; scramblase; single particle profiling; class a; signaling receptor; switch control |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 300 |
| Issue: | 2 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2024-02-01 |
| Start Page: | 105649 |
| Language: | English |
| DOI: | 10.1016/j.jbc.2024.105649 |
| PUBMED: | 38237683 |
| PROVIDER: | scopus |
| PMCID: | PMC10874734 |
| DOI/URL: | |
| Notes: | Source: Scopus |
