Secretory vesicular transport from the Golgi is altered during ATP-binding cassette protein A1 (ABCA1)-mediated cholesterol efflux.
Apolipoprotein AI (apoAI)-mediated cholesterol efflux is a process by which cells export excess cellular cholesterol to apoAI to form high density lipoprotein. ATP-binding cassette protein A1 (ABCA1) has recently been identified as the key regulator of this process. The pathways of intracellular cholesterol transport during efflux are largely unknown nor is the molecular mechanism by which ABCA1 governs cholesterol efflux well understood. Here, we report that, in both macrophages and fibroblasts, the secretory vesicular transport changes in response to apoAI-mediated cholesterol efflux. Vesicular transport from the Golgi to the plasma membrane increased 2-fold during efflux. This increase in vesicular transport during efflux was observed in both raft-poor and raft-rich vesicle populations originated from the Golgi. Importantly, enhanced vesicular transport in response to apoAI is absent in Tangier fibroblasts, a cell type with deficient cholesterol efflux due to functional ABCA1 mutations. These findings are consistent with an efflux model whereby cholesterol is transported from the storage site to the plasma membrane via the Golgi. ABCA1 may influence cholesterol efflux in part by enhancing vesicular trafficking from the Golgi to the plasma membrane.
Zha
Xiaohui
X
Lipoprotein & Atherosclerosis Group, University of Ottawa Heart Institute, Ontario K1Y 4W7, Canada.
Gauthier
Andre
A
Genest
Jacques
J
McPherson
Ruth
R
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology; D001692:Biological Transport; D020126:Brefeldin A / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D022142:Secretory Vesicles / Q000502:physiology*
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D017261:Glycosylphosphatidylinositols; D020126:Brefeldin A; D002784:Cholesterol