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

Etienne Morel (1) , Sara Ghezzal (1) , Géraldine Lucchi (2, 3) , Caroline Truntzer (2) , Jean-Paul Pais de Barros (4, 5) , Françoise Simon-Plas (6) , Sylvie Demignot (1, 7) , Chieko Mineo (8) , Philip Shaul , Armelle Leturque (1) , Monique Rousset (1) , Véronique Carrière (1, 7)

1 CRC - Centre de Recherche des Cordeliers
2 CLIPP - Plate-forme Protéomique CLIPP - Clinical and Innovation Proteomic Platform [Dijon]
3 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
4 LAP - Plateforme Lipidomique [Dijon]
5 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
6 Agroécologie [Dijon]
7 CRSA - Centre de Recherche Saint-Antoine
8 Center for Pulmonary and Vascular Biology : Department of Pediatrics [University of Texas, Southwestern Medical Center, Dallas]

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: scavenger receptor; cholesterol; lipid raft; sphingolipid; lipid trafficking

Domaines: Biochimie, Biologie Moléculaire

Etienne Morel, Sara Ghezzal, Géraldine Lucchi, Caroline Truntzer, Jean-Paul Pais de Barros, et al.. Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells. Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 2018, 1863 (2), pp.199-211. ⟨10.1016/j.bbalip.2017.11.009⟩. ⟨hal-01661856⟩