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

Etienne Morel, Sara Ghezzal, Géraldine Lucchi, Caroline Truntzer, Jean Paul Pais de Barros, Françoise Simon-Plas, Sylvie Demignot, Chieko Mineo, Philip W. Shaul, Armelle Leturque, Monique Rousset, Véronique Carrière

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)199-211
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1863
Issue number2
DOIs
StatePublished - Feb 2018

Keywords

  • Cholesterol
  • Lipid raft
  • Lipid trafficking
  • Scavenger receptor
  • Sphingolipid

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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