Le Lay, SoazigRodriguez, MacarenaJessup, WendyRentero Alfonso, CarlesLi, QiongCartland, SiânGrewal, ThomasGaus, Katharina2018-06-112018-06-112011-08-121932-6203https://hdl.handle.net/2445/122890Caveolin-1 (Cav1), a structural protein required for the formation of invaginated membrane domains known as caveolae, has been implicated in cholesterol trafficking and homeostasis. Here we investigated the contribution of Cav1 to apolipoprotein A-I (apoA-I) cell surface binding and intracellular processing using mouse embryonic fibroblasts (MEFs) derived from wild type (WT) or Cav1-deficient (Cav1−/−) animals. We found that cells expressing Cav1 have 2.6-fold more apoA-I binding sites than Cav1−/− cells although these additional binding sites are not associated with detergent-free lipid rafts. Further, Cav1-mediated binding targets apoA-I for internalization and degradation and these processes are not correlated to cholesterol efflux. Despite lower apoA-I binding, cholesterol efflux from Cav1−/− MEFs is 1.7-fold higher than from WT MEFs. Stimulation of ABCA1 expression with an LXR agonist enhances cholesterol efflux from both WT and Cav1−/− cells without increasing apoA-I surface binding or affecting apoA-I processing. Our results indicate that there are at least two independent lipid binding sites for apoA-I; Cav1-mediated apoA-I surface binding and uptake is not linked to cholesterol efflux, indicating that membrane domains other than caveolae regulate ABCA1-mediated cholesterol efflux.11 p.application/pdfengcc-by (c) Le Lay, Soazig et al., 2011http://creativecommons.org/licenses/by/3.0/esColesterolMembranes cel·lularsCholesterolCell membranesinfo:eu-repo/semantics/article6716202018-06-11info:eu-repo/semantics/openAccess21858084