Cellular Localization and Trafficking of the Human ABCG1 Transporter
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 ap...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-11-01
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| Series: | Biology |
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| Online Access: | http://www.mdpi.com/2079-7737/3/4/781 |
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| author | Edward B. Neufeld Katherine O'Brien Avram D. Walts John A. Stonik Steven J. Demosky Daniela Malide Christian A. Combs Alan T. Remaley |
| author_facet | Edward B. Neufeld Katherine O'Brien Avram D. Walts John A. Stonik Steven J. Demosky Daniela Malide Christian A. Combs Alan T. Remaley |
| author_sort | Edward B. Neufeld |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T09:09:10Z |
| format | Article |
| id | doaj.art-a0d5da5cd5484533aadedc573e9665c8 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-12T09:09:10Z |
| publishDate | 2014-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-a0d5da5cd5484533aadedc573e9665c82023-09-02T15:05:18ZengMDPI AGBiology2079-77372014-11-013478180010.3390/biology3040781biology3040781Cellular Localization and Trafficking of the Human ABCG1 TransporterEdward B. Neufeld0Katherine O'Brien1Avram D. Walts2John A. Stonik3Steven J. Demosky4Daniela Malide5Christian A. Combs6Alan T. Remaley7Lipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USALipid Trafficking Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USALipid Trafficking Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USALipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USALipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANHLBI Light Microscopy Core Facility, National Institutes of Health, Bethesda, MD 20892, USANHLBI Light Microscopy Core Facility, National Institutes of Health, Bethesda, MD 20892, USALipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAWe 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.http://www.mdpi.com/2079-7737/3/4/781ABCG1cholesterolcholesterol effluxvesicular traffickingHDLrescretion |
| spellingShingle | Edward B. Neufeld Katherine O'Brien Avram D. Walts John A. Stonik Steven J. Demosky Daniela Malide Christian A. Combs Alan T. Remaley Cellular Localization and Trafficking of the Human ABCG1 Transporter Biology ABCG1 cholesterol cholesterol efflux vesicular trafficking HDL rescretion |
| title | Cellular Localization and Trafficking of the Human ABCG1 Transporter |
| title_full | Cellular Localization and Trafficking of the Human ABCG1 Transporter |
| title_fullStr | Cellular Localization and Trafficking of the Human ABCG1 Transporter |
| title_full_unstemmed | Cellular Localization and Trafficking of the Human ABCG1 Transporter |
| title_short | Cellular Localization and Trafficking of the Human ABCG1 Transporter |
| title_sort | cellular localization and trafficking of the human abcg1 transporter |
| topic | ABCG1 cholesterol cholesterol efflux vesicular trafficking HDL rescretion |
| url | http://www.mdpi.com/2079-7737/3/4/781 |
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