title: Interaction abolishment between mutant caveolin-1(Δ62-100) and ABCA1 reduces HDL-mediated cellular cholesterol efflux.
abstract: Our previous study shows that caveolin-1 colocalizes and interacts with ATP-binding cassette transporter A1 (ABCA1), which is intimately involved in cellular cholesterol efflux. In this study, we further clarified the region of caveolin-1 that interacts with ABCA1. We also examined the interaction between mutant caveolin-1 and ABCA1 in HDL-mediated cholesterol efflux. We constructed a panel of mutant caveolin-1 proteins and co-transfected them into rat aortic endothelial and human embryonic kidney 293 (HEK293) cells. The co-immunoprecipitation shows that mutant oligomerization domain of caveolin-1, caveolin-1(Δ62-100), is required for the interaction of caveolin-1 with ABCA1. Caveolin-1(Δ62-100) did not colocalize with ABCA1 in the cholesterol-loaded cells after HDL incubation as observed by immunofluorescence confocal microscopy. Concomitantly, caveolin-1(Δ62-100) suppressed HDL-mediated cholesterol efflux. The results suggest that the region of caveolin-1 between amino acids 62 and 100 is an oligomerization domain as well as an attachment site for ABCA1 interaction that regulates HDL-mediated cholesterol efflux.
authors.affiliation: Department of Life Science, Tunghai University, Taichung, Taiwan, ROC.
authors.forename: Chan-Yen
authors.initials: CY
authors.lastname: Kuo
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Jaw-Ji
authors.initials: JJ
authors.lastname: Yang
authors.forename: Vivian C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017384:Sequence Deletion
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C495540:CAV1 protein, human; D051242:Caveolin 1; D008075:Lipoproteins, HDL; D002784:Cholesterol