High circulating levels of the "good cholesterol" HDL are associated with decreased risk of cardiovascular disease. HDL helps the liver excrete extra cholesterol by binding to a receptor in the liver called scavenger receptor-BI (SR-BI). However, the signaling events between HDL and SR-BI that afforded heart healthy benefits were not known.
In a study appearing online on March 24, in advance of the April 1 print edition of the Journal of Clinical Investigation, Philip Shaul and colleagues from the University of Texas Southwestern Medical Center examine this pathway.
The authors show that HDL activates an enzyme called eNOS and sets off a cellular signal that depends on cholesterol efflux and two intact domains of SR-BI -- the transmembrane domain and its cytoplasmic tail. These regions of SR-BI may serve as "cholesterol sensors" which set into motion cellular events to activate eNOS. This may be the mechanism responsible for the ability of HDL to reduce cardiovascular disease risk.
TITLE: Cholesterol binding, efflux, and a PDZ-interacting domain of scavenger receptor--BI mediate HDL-initiated signaling
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