The involvement of membrane vesiculation in ABCA1 mediated efflux

Abstract

The mechanism of ATP binding cassette transporter A1 (ABCA1) mediated cholesterol efflux is presently unclear. Cells expressing ABCA1 reported to display distinctive membrane-protrusion-like morphology and apoA1 was also seen to bind to those structures. We hypothesized that cholesterol efflux may be in part originated from membrane shedding through membrane vesiculation and therefore may rely on relatively flexible plasma membrane. We tested several reagents known to modulate membrane fluidity and found that cholesterol efflux is indeed inversely correlated with membrane rigidity. Additionally, using differential ultracentrifugation, we provide evidence that, during ABCA1 mediated cholesterol efflux, cells produce a significant quantity of apoA1 free membrane vesicles along with apoA1 containing lipoproteins. This process can be inhibited by rigidifying the plasma membrane. We therefore conclude that flexibility of plasma membrane is necessary for ABCA1 mediated cholesterol efflux and speculate that ABCA1 and apoA1 work together to secrete membrane vesicles during efflux.