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Saddar, Sonika; Carriere, Véronique; Lee, Wan-Ru; Tanigaki, Keiji; Yuhanna, Ivan S.; Parathath, Sajesh; Morel, Etienne; Warrier, Manya; Sawyer, Janet K.; Gerard, Robert D.; Temel, Ryan E.; Brown, J. Mark; Connelly, Margery; Mineo, Chieko; Shaul, Philip W.

Scavenger Receptor Class B Type I Is a Plasma Membrane Cholesterol Sensor

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  • Medientyp: E-Artikel
  • Titel: Scavenger Receptor Class B Type I Is a Plasma Membrane Cholesterol Sensor
  • Beteiligte: Saddar, Sonika; Carriere, Véronique; Lee, Wan-Ru; Tanigaki, Keiji; Yuhanna, Ivan S.; Parathath, Sajesh; Morel, Etienne; Warrier, Manya; Sawyer, Janet K.; Gerard, Robert D.; Temel, Ryan E.; Brown, J. Mark; Connelly, Margery; Mineo, Chieko; Shaul, Philip W.
  • Erschienen: Ovid Technologies (Wolters Kluwer Health), 2013
  • Erschienen in: Circulation Research
  • Sprache: Englisch
  • DOI: 10.1161/circresaha.112.280081
  • ISSN: 1524-4571; 0009-7330
  • Schlagwörter: Cardiology and Cardiovascular Medicine ; Physiology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec> <jats:title> <jats:underline>Rationale:</jats:underline> </jats:title> <jats:p>Signal initiation by the high-density lipoprotein (HDL) receptor scavenger receptor class B, type I (SR-BI), which is important to actions of HDL on endothelium and other processes, requires cholesterol efflux and the C-terminal transmembrane domain. The C-terminal transmembrane domain uniquely interacts with plasma membrane (PM) cholesterol.</jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Objective:</jats:underline> </jats:title> <jats:p>The molecular basis and functional significance of SR-BI interaction with PM cholesterol are unknown. We tested the hypotheses that the interaction is required for SR-BI signaling, and that it enables SR-BI to serve as a PM cholesterol sensor.</jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Methods and Results:</jats:underline> </jats:title> <jats:p>In studies performed in COS-M6 cells, mutation of a highly conserved C-terminal transmembrane domain glutamine to alanine (SR-BI-Q445A) decreased PM cholesterol interaction with the receptor by 71% without altering HDL binding or cholesterol uptake or efflux, and it yielded a receptor incapable of HDL-induced signaling. Signaling prompted by cholesterol efflux to methyl-β-cyclodextrin also was prevented, indicating that PM cholesterol interaction with the receptor enables it to serve as a PM cholesterol sensor. Using SR-BI-Q445A, we further demonstrated that PM cholesterol sensing by SR-BI does not influence SR-BI-mediated reverse cholesterol transport to the liver in mice. However, the PM cholesterol sensing does underlie apolipoprotein B intracellular trafficking in response to postprandial micelles or methyl-β-cyclodextrin in cultured enterocytes, and it is required for HDL activation of endothelial NO synthase and migration in cultured endothelial cells and HDL-induced angiogenesis in vivo.</jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Conclusions:</jats:underline> </jats:title> <jats:p>Through interaction with PM cholesterol, SR-BI serves as a PM cholesterol sensor, and the resulting intracellular signaling governs processes in both enterocytes and endothelial cells.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang