The ABCA1 transporter functions both in cellular cholesterol trafficking and in plasma membrane cholesterol efflux. ABCA1 expression re-distributes cholesterol in the plasma membrane, resulting in expansion of non-raft domains with which apoA-I preferentially associates (Zha et al. 2001; Landry et al. 2006) . In addition, secretory vesicular transport from the Golgi is enhanced by stimulation of choles-terol efflux by apoA-I in normal cells, but not in Tangier cells with deficient cho-lesterol efflux due to inactive ABCA1 (Zha et al. 2003) . Structural and functional abnormalities in caveolar processing and in the trans -Golgi secretory network have been reported in cells lacking functional ABCA1, which indicates that the activity of this transporter affects the vesicular budding between the Golgi and the plasma membrane (Orsó et al. 2000) . Together, these findings indicate that ABCA1 func-tions to promote vesicular trafficking of membranes in the secretory pathway and contributes to the flow of lipids from intracellular storage sites to the plasma mem-brane via the Golgi (Zha et al. 2003) . These observations may link ABCA1 activity with the mobilization of lipids from LD to the ER and subsequent trafficking via the Golgi to the plasma membrane for lipid efflux. It is tempting to speculate that Rab18, which tethers the LD to the ER, may be involved in regulating the delivery of LD-associated cholesterol to the ER for its subsequent ensuing trafficking through the Golgi to the plasma membrane for efflux.
3.12 Conclusions
Cellular lipid traffic and homeostasis integrates the regulation of cellular lipid metabolism with cellular lipid uptake and with cellular lipid export. We empha-size here that lipid and particularly cholesterol traffic are intimately linked to lipid secretion and efflux. The coordinated regulation of cholesterol efflux pathways starts with de novo synthesis of cholesterol and lipoprotein uptake and with their cellular traffic by vesicular and molecular transport mechanisms, which together with extracellular lipid acceptors control the transporters involved in cellular export.
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