ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis
Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally di...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520314036 |
| _version_ | 1818406311638859776 |
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| author | Yoshio Yamauchi Shinji Yokoyama Ta-Yuan Chang |
| author_facet | Yoshio Yamauchi Shinji Yokoyama Ta-Yuan Chang |
| author_sort | Yoshio Yamauchi |
| collection | DOAJ |
| description | Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway. |
| first_indexed | 2024-12-14T09:09:56Z |
| format | Article |
| id | doaj.art-bcf7b70039f34c40bd8474fe8f4804c3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T09:09:56Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-bcf7b70039f34c40bd8474fe8f4804c32022-12-21T23:08:36ZengElsevierJournal of Lipid Research0022-22752016-01-015717788ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesisYoshio Yamauchi0Shinji Yokoyama1Ta-Yuan Chang2To whom correspondence should be addressed.; Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755Nutritional Health Science Research Center and Department of Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, JapanTo whom correspondence should be addressed.; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway.http://www.sciencedirect.com/science/article/pii/S0022227520314036ATP binding cassette transporter A1acyl-CoA:cholesterol acyltransferasecholesterol/effluxcholesterol/traffickinghigh density lipoproteinlipid rafts |
| spellingShingle | Yoshio Yamauchi Shinji Yokoyama Ta-Yuan Chang ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis Journal of Lipid Research ATP binding cassette transporter A1 acyl-CoA:cholesterol acyltransferase cholesterol/efflux cholesterol/trafficking high density lipoprotein lipid rafts |
| title | ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis |
| title_full | ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis |
| title_fullStr | ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis |
| title_full_unstemmed | ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis |
| title_short | ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis |
| title_sort | abca1 dependent sterol release sterol molecule specificity and potential membrane domain for hdl biogenesis |
| topic | ATP binding cassette transporter A1 acyl-CoA:cholesterol acyltransferase cholesterol/efflux cholesterol/trafficking high density lipoprotein lipid rafts |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520314036 |
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