Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells

• Published in: Biochimica et biophysica acta 2018-02, Vol.1863 (2), p.199-211
• Main Authors: Morel, Etienne, Ghezzal, Sara, Lucchi, Géraldine, Truntzer, Caroline, Pais de Barros, Jean-Paul, Simon-Plas, Françoise, Demignot, Sylvie, Mineo, Chieko, Shaul, Philip W., Leturque, Armelle, Rousset, Monique, Carrière, Véronique
• Format: Article
• Language: English
• Subjects: Biochemistry, Molecular Biology; Caco-2 Cells; Cholesterol; Cholesterol - metabolism; Epithelial Cells - metabolism; Humans; Intestinal Mucosa - metabolism; Life Sciences; Lipid Droplets - metabolism; Lipid raft; Lipid trafficking; Lysophospholipids - metabolism; Membrane Microdomains - metabolism; Scavenger receptor; Scavenger Receptors, Class B - metabolism; Signal Transduction - physiology; Sphingolipid; Sphingomyelins - metabolism
• ISSN: 1388-1981; 0006-3002; 1879-2618; 1878-2434
• DOI: 10.1016/j.bbalip.2017.11.009

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. •SR-B1-dependent lipid sensing is associated with cholesterol trafficking.•Changes in raft-like lipid and protein composition occurs during this sensing.•Identification of cellular processes driven by SR-B1