Model of the role of membrane domains in apoA-I-mediated cholesterol efflux.

<p>Predominantly saturated phospholipids (color red and yellow) and cholesterol (yellow squares) form domains (lipid rafts, caveolae) that are distinct from more fluid, non-raft domains (grey lipids). <b>A.</b> High-capacity apoA-I binding sites preferentially form at the raft/non-raft border where disordered lipid packing creates space for the insertion of apoA-I's amphipathic α-helices between the phospholipids polar head groups. <b>B.</b> Caveolae at the plasma membrane form a ring of high membrane curvature at its neck to which apoA-I may bind with high capacity. ApoA-I bound at the caveolae neck is targeted for internalization and degradation (dashed arrow) and is not required for lipid efflux (grey arrow) <b>C.</b> ABCA1 expression does not mediate high capacity apoA-I binding sites. Stimulation of ABCA1 translocase activity by apoA-I facilitates efflux (solid black arrow) and may create additional apoA-I binding sites.