Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.
Fiche publication
Date publication
février 2018
Journal
Biochimica et biophysica acta
Auteurs
Membres identifiés du Cancéropôle Est :
Mme TRUNTZER Caroline, Dr PAIS DE BARROS Jean-Paul
Tous les auteurs :
Morel E, Ghezzal S, Lucchi G, Truntzer C, Pais de Barros JP, Simon-Plas F, Demignot S, Mineo C, Shaul PW, Leturque A, Rousset M, Carrière V
Lien Pubmed
Résumé
Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics.
Mots clés
Caco-2 Cells, Cholesterol, metabolism, Epithelial Cells, metabolism, Humans, Intestinal Mucosa, metabolism, Lipid Droplets, metabolism, Lysophospholipids, metabolism, Membrane Microdomains, metabolism, Scavenger Receptors, Class B, metabolism, Signal Transduction, physiology, Sphingomyelins, metabolism
Référence
Biochim. Biophys. Acta. 2018 02;1863(2):199-211