Abstract
Nascent HDL is known to be formed by the interaction of apolipoprotein A-I (apoA-I) with transmembrane ABCA1, but the molecular mechanism by which nascent HDL forms is less well understood. Here, we studied how reconstituted high density lipoprotein (rHDL) forms spontaneously on the interaction of apoA-I with model membranes. The formation of rHDL from pure phosphatidylcholine (PC) large unilamellar vesicles (LUVs) proceeded very slowly at 37.0 degrees C, but sphingomyelin (SM) -rich PC/SM LUVs, which are in a gel/liquid-disordered phase (L(d) phase) at this temperature, were rapidly microsolubilized to form rHDL by apoA-I. The addition of cholesterol decreased the rate at which rHDL formed and induced the selective extraction of lipids by apoA-I, which preferably extracted lipids of L(d) phase rather than lipids of liquid-ordered phase. In addition, apoA-I extracted lipids from the outer and inner leaflets of LUVs simultaneously. These results suggest that the heterogeneous interface of the mixed membranes facilitates the insertion of apoA-I and induces L(d) phase-selective but leaflet-nonselective lipid extraction to form rHDL; they are compatible with recent cell works on apoA-I-dependent HDL generation.
Highlights
Nascent HDL is known to be formed by the interaction of apolipoprotein A-I with transmembrane ABCA1, but the molecular mechanism by which nascent HDL forms is less well understood
In the case of pure SM large unilamellar vesicle (LUV), a sharp decrease in brÀDPH was observed at ?41jC, in good agreement with a previous report [33]. This sharp change in brÀDPH shifted to lower temperatures and became broader as the PC molar fraction in PC/ SM LUVs increased, suggesting a decrease in the cooperativity of the transition and an increase in the temperature range of the gel/Ld phase
Close to the experimental temperatures of 33.0jC and 37.0jC. These results indicated that spontaneous solubilization of LUVs by apolipoprotein A-I (apoA-I) was accelerated when the membrane was in a state of two-phase coexistence
Summary
Nascent HDL is known to be formed by the interaction of apolipoprotein A-I (apoA-I) with transmembrane ABCA1, but the molecular mechanism by which nascent HDL forms is less well understood. We assume that disruption of the plasma membrane by ABCA1 spontaneously induces the extraction of lipids and the formation of nascent HDL by apoA-I.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
