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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kobayashi, Toshihide Chang, Catherine C. Y. Furukawa, Koichi Ueda, Kazumitsu Kishimoto, Takuma Abe-dohmae, Sumiko Yamauchi, Yoshio Chang, Ta-yuan Rogers, Maximillian A. Yokoyama, Shinji Fujimoto, Toyoshi Ishigami, Masato Iwamoto, Noriyuki |
| Description | Author Affiliation: Yamauchi Y ( From the Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan, yyoshio@med.nagoya-u.ac.jp.); Iwamoto N ( the Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.); Rogers MA ( the Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755.); Abe-Dohmae S ( the Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.); Fujimoto T ( the Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.); Chang CC ( the Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755.); Ishigami M ( the Institute for Integrated Cell-Material Sciences and Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.); Kishimoto T ( the Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198, Japan, and.); Kobayashi T ( the Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198, Japan, and.); Ueda K ( the Institute for Integrated Cell-Material Sciences and Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.); Furukawa K ( From the Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.); Chang TY ( the Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, Ta.Yuan.Chang@Dartmouth.edu.); Yokoyama S ( the Nutritional Health Science Research Center and Department of Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.) |
| Abstract | Cellular cholesterol homeostasis involves sterol sensing at the endoplasmic reticulum (ER) and sterol export from the plasma membrane (PM). Sterol sensing at the ER requires efficient sterol delivery from the PM; however, the macromolecules that facilitate retrograde sterol transport at the PM have not been identified. ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol and phospholipid export to apolipoprotein A-I for the assembly of high density lipoprotein (HDL). Mutations in ABCA1 cause Tangier disease, a familial HDL deficiency. Several lines of clinical and experimental evidence suggest a second function of ABCA1 in cellular cholesterol homeostasis in addition to mediating cholesterol efflux. Here, we report the unexpected finding that ABCA1 also plays a key role in facilitating retrograde sterol transport from the PM to the ER for sterol sensing. Deficiency in ABCA1 delays sterol esterification at the ER and activates the SREBP-2 cleavage pathway. The intrinsic ATPase activity in ABCA1 is required to facilitate retrograde sterol transport. ABCA1 deficiency causes alternation of PM composition and hampers a clathrin-independent endocytic activity that is required for ER sterol sensing. Our finding identifies ABCA1 as a key macromolecule facilitating bidirectional sterol movement at the PM and shows that ABCA1 controls retrograde sterol transport by modulating a certain clathrin-independent endocytic process. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 39 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-09-25 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | ATP Binding Cassette Transporter 1 Metabolism Endoplasmic Reticulum Sterols Animals Biological Transport Cells, Cultured Lipid Metabolism Mice Sterol Regulatory Element Binding Protein 2 Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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