Single-molecule analysis of ABCA1 dimerization mechanism during HDL production

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18681
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied biochemistry
• Research Institution: Kyoto University
• Principal Investigator: NAGATA Koh 京都大学, 物質－細胞統合システム拠点, 特別研究員(RPD) (70401213)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: HDL / 善玉コレステロール / ABCタンパク質 / ABCA1 / 1分子イメージング / ダイマー

Outline of Final Research Achievements

To prevent and treat atherosclerosis, it is important to elucidate the mechanism underlying the production of HDL, also known as good cholesterol. In the present study, we observed ABCA1, a membrane protein which is essential for HDL production, by TIRF microscope. We found that C-terminal leucine zipper-like motif of ABCA1 is involved in its dimerization on the plasma membrane. HDL particles produced by a mutant ABCA1 lacking this motif showed different profiles compared with those by wild type ABCA1. We also clarified that ABCA1 is less likely to dimerize in the presence of PSC833, a drug which inhibits cholesterol efflux by ABCA1. In addition, ABCA7, which is highly homologous to ABCA1, was found to exist mainly as monomers. Recently, it is widely accepted that HDL quality is as important as its quantity to prevent atherosclerosis. Our results suggest that ABCA1 dimerization contributes to controlling HDL quality.

Free Research Field

細胞生物学、生化学