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ABCA1 Mediates Unfolding of Apolipoprotein AI N Terminus on the Cell Surface Before Lipidation and Release of Nascent High-Density Lipoprotein
| Content Provider | Scilit |
|---|---|
| Author | Wang, Shuhui Gulshan, Kailash Brubaker, Gregory Hazen, Stanley L. Smith, Jonathan D. |
| Copyright Year | 2013 |
| Description | Journal: Arteriosclerosis, thrombosis, and vascular biology Objective— To gain insight into the mechanism by which ABCA1 generates nascent high-density lipoprotein. Approach and Results— HEK293 cells were stably transfected with ABCA1 vectors, encoding wild type, and the W590S and C1477R Tangier disease mutation isoforms, along with the K939M ATP-binding domain mutant. Apolipoprotein AI (ApoAI) binding, plasma membrane remodeling, cholesterol efflux, apoAI cell surface unfolding, and apoAI cell surface lipidation were determined, the latter 2 measured using novel fluorescent apoAI indicators. The W590S isoform had decreased plasma membrane remodeling and lipid efflux activities, and the C1477R isoform had decreased apoAI binding, and lipid efflux activities, whereas the K939M isoform did not bind apoAI, remodel the membrane, or efflux cholesterol. However, all ABCA1 isoforms led to apoAI unfolding at the cell surface, which was higher for the isoforms that increased apoAI binding. ApoAI lipidation was not detected on ABCA1-expressing cells, only in the conditioned medium, consistent with rapid release of nascent high-density lipoprotein from ABCA1-expressing cells. Conclusions— We identified a third activity of ABCA1, the ability to unfold the N terminus of apoAI on the cell surface. Our results support a model in which unfolded apoAI on the cell surface is an intermediate in its lipidation and that, once apoAI is lipidated, it forms an unstable structure that is rapidly released from the cells to generate high-density lipoprotein. |
| Related Links | https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.112.301195 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701943/pdf https://www.ahajournals.org/doi/reader/10.1161/ATVBAHA.112.301195 |
| Ending Page | 1205 |
| Page Count | 9 |
| Starting Page | 1197 |
| ISSN | 10795642 |
| e-ISSN | 15244636 |
| DOI | 10.1161/atvbaha.112.301195 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Issue Number | 6 |
| Volume Number | 33 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2013-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Arteriosclerosis, thrombosis, and vascular biology Biochemistry and Molecular Biology Nascent High-density Lipoprotein Apolipoprotein Ai Unfolding Reverse Cholesterol Transport |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
