Unknown

Dataset Information

0

ABCA1 dimer-monomer interconversion during HDL generation revealed by single-molecule imaging.


ABSTRACT: The generation of high-density lipoprotein (HDL), one of the most critical events for preventing atherosclerosis, is mediated by ATP-binding cassette protein A1 (ABCA1). ABCA1 is known to transfer cellular cholesterol and phospholipids to apolipoprotein A-I (apoA-I) for generating discoidal HDL (dHDL) particles, composed of 100-200 lipid molecules surrounded by two apoA-I molecules; however, the regulatory mechanisms are still poorly understood. Here we observed ABCA1-GFP and apoA-I at the level of single molecules on the plasma membrane via a total internal reflection fluorescence microscope. We found that about 70% of total ABCA1-GFP spots are immobilized on the plasma membrane and estimated that about 89% of immobile ABCA1 molecules are in dimers. Furthermore, an ATPase-deficient ABCA1 mutant failed to be immobilized or form a dimer. We found that the lipid acceptor apoA-I interacts with the ABCA1 dimer to generate dHDL and is followed by ABCA1 dimer-monomer interconversion. This indicates that the formation of the ABCA1 dimer is the key for apoA-I binding and nascent HDL generation. Our findings suggest the physiological significance of conversion of the ABCA1 monomer to a dimer: The dimer serves as a receptor for two apoA-I molecules for dHDL particle generation.

SUBMITTER: Nagata KO 

PROVIDER: S-EPMC3612634 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

ABCA1 dimer-monomer interconversion during HDL generation revealed by single-molecule imaging.

Nagata Koh O KO   Nakada Chieko C   Kasai Rinshi S RS   Kusumi Akihiro A   Ueda Kazumitsu K  

Proceedings of the National Academy of Sciences of the United States of America 20130311 13


The generation of high-density lipoprotein (HDL), one of the most critical events for preventing atherosclerosis, is mediated by ATP-binding cassette protein A1 (ABCA1). ABCA1 is known to transfer cellular cholesterol and phospholipids to apolipoprotein A-I (apoA-I) for generating discoidal HDL (dHDL) particles, composed of 100-200 lipid molecules surrounded by two apoA-I molecules; however, the regulatory mechanisms are still poorly understood. Here we observed ABCA1-GFP and apoA-I at the level  ...[more]

Similar Datasets

| S-EPMC3443179 | biostudies-literature
| S-EPMC4689340 | biostudies-literature
| S-EPMC5906560 | biostudies-literature
| S-EPMC2582371 | biostudies-literature
| S-EPMC4357730 | biostudies-literature
| S-EPMC6232968 | biostudies-literature
| S-EPMC4968397 | biostudies-literature
| S-EPMC3912175 | biostudies-literature
| S-EPMC8085067 | biostudies-literature
| S-EPMC2527093 | biostudies-literature