title: Cellular Localization and Trafficking of the Human ABCG1 Transporter.
abstract: We have developed a suitable heterologous cell expression system to study the localization, trafficking, and site(s) of function of the human ABCG1 transporter. Increased plasma membrane (PM) and late endosomal (LE) cholesterol generated by ABCG1 was removed by lipoproteins and liposomes, but not apoA-I. Delivery of ABCG1 to the PM and LE was required for ABCG1-mediated cellular cholesterol efflux. ABCG1 LEs frequently contacted the PM, providing a collisional mechanism for transfer of ABCG1-mobilized cholesterol, similar to ABCG1-mediated PM cholesterol efflux to lipoproteins. ABCG1-mobilized LE cholesterol also trafficked to the PM by a non-vesicular pathway. Transfer of ABCG1-mobilized cholesterol from the cytoplasmic face of LEs to the PM and concomitant removal of cholesterol from the outer leaflet of the PM bilayer by extracellular acceptors suggests that ABCG1 mobilizes cholesterol on both sides of the lipid bilayer for removal by acceptors. ABCG1 increased uptake of HDL into LEs, consistent with a potential ABCG1-mediated cholesterol efflux pathway involving HDL resecretion. Thus, ABCG1 at the PM mobilizes PM cholesterol and ABCG1 in LE/LYS generates mobile pools of cholesterol that can traffic by both vesicular and non-vesicular pathways to the PM where it can also be transferred to extracellular acceptors with a lipid surface.
authors.affiliation: Lipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. neufelde@mail.nih.gov.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Neufeld
authors.affiliation: Lipid Trafficking Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. obrienk@nhlbi.nih.gov.
authors.forename: Katherine
authors.initials: K
authors.lastname: O'Brien
authors.affiliation: Lipid Trafficking Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. awalts@yahoo.com.
authors.forename: Avram D
authors.initials: AD
authors.lastname: Walts
authors.affiliation: Lipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. jstonik@verizon.net.
authors.forename: John A
authors.initials: JA
authors.lastname: Stonik
authors.affiliation: Lipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. sjdjr@nhlbi.nih.gov.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Demosky
authors.affiliation: NHLBI Light Microscopy Core Facility, National Institutes of Health, Bethesda, MD 20892, USA. dmalide@mail.nih.gov.
authors.forename: Daniela
authors.initials: D
authors.lastname: Malide
authors.affiliation: NHLBI Light Microscopy Core Facility, National Institutes of Health, Bethesda, MD 20892, USA. combsc@nih.gov.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Combs
authors.affiliation: Lipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Alan.Remaley@nih.gov.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley