ATP‐binding cassette transporters and sterol O ‐acyltransferases interact at membrane microdomains to modulate sterol uptake and esterification
| Autor: | Estela Area-Gomez, Heimo Wolinski, Kelly V. Ruggles, Christine S. Kim, Joseph A. DeGiorgis, Igor Stagljar, Dina A. Balderes, Zhongmin A. Guo, Eric A. Schon, Lisa Wilcox, Sonia Gulati, Jamie Snider, Juliana T. Granato, Sepp D. Kohlwein, Stephen L. Sturley |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Lipoproteins Sterol O-acyltransferase ATP-binding cassette transporter Saccharomyces cerevisiae Biochemistry Research Communication Mice 03 medical and health sciences chemistry.chemical_compound Membrane Microdomains 0302 clinical medicine Lipid droplet polycyclic compounds Genetics Animals Molecular Biology ATP Binding Cassette Transporter Subfamily G Member 1 030304 developmental biology 0303 health sciences Esterification Sterol transport Sterol Sterol regulatory element-binding protein Sterols chemistry Acyltransferases Cholesteryl ester ATP-Binding Cassette Transporters lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery Sterol O-Acyltransferase Biotechnology |
| Zdroj: | The FASEB Journal. 29:4682-4694 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | A key component of eukaryotic lipid homeostasis is the esterification of sterols with fatty acids by sterol O-acyltransferases (SOATs). The esterification reactions are allosterically activated by their sterol substrates, the majority of which accumulate at the plasma membrane. We demonstrate that in yeast, sterol transport from the plasma membrane to the site of esterification is associated with the physical interaction of the major SOAT, acyl-coenzyme A:cholesterol acyltransferase (ACAT)-related enzyme (Are)2p, with 2 plasma membrane ATP-binding cassette (ABC) transporters: Aus1p and Pdr11p. Are2p, Aus1p, and Pdr11p, unlike the minor acyltransferase, Are1p, colocalize to sterol and sphingolipid-enriched, detergent-resistant microdomains (DRMs). Deletion of either ABC transporter results in Are2p relocalization to detergent-soluble membrane domains and a significant decrease (53–36%) in esterification of exogenous sterol. Similarly, in murine tissues, the SOAT1/Acat1 enzyme and activity localize to DRMs. This subcellular localization is diminished upon deletion of murine ABC transporters, such as Abcg1, which itself is DRM associated. We propose that the close proximity of sterol esterification and transport proteins to each other combined with their residence in lipid-enriched membrane microdomains facilitates rapid, high-capacity sterol transport and esterification, obviating any requirement for soluble intermediary proteins.—Gulati, S., Balderes, D., Kim, C., Guo, Z. A., Wilcox, L., Area-Gomez, E., Snider, J., Wolinski, H., Stagljar, I., Granato, J. T., Ruggles, K. V., DeGiorgis, J. A., Kohlwein, S. D., Schon, E. A., Sturley, S. L. ATP-binding cassette transporters and sterol O-acyltransferases interact at membrane microdomains to modulate sterol uptake and esterification. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text