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 Geraldine Lucchi 2 Caroline Truntzer 2 Jean-Paul Pais de Barros 3, 4 Françoise Simon-Plas 5 Sylvie Demignot 1 Chieko Mineo 6 Philip W Shaul 6 Armelle Leturque 1 Monique Rousset 1 Véronique Carriere 1, *
* Auteur correspondant
2 CLIPP - Plate-forme Protéomique CLIPP - Clinical and Innovation Proteomic Platform [Dijon]
FEMTO-ST - Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies, ICMUB - Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon]
3 LAP - Plateforme Lipidomique [Dijon]
LNC - Lipides - Nutrition - Cancer (U866), IFR100 - Structure fédérative de recherche Santé-STIC, CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
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.
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Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, Elsevier, 2018, 1863 (2), pp.199-211. 〈http://www.sciencedirect.com/science/article/pii/S1388198117302330〉. 〈10.1016/j.bbalip.2017.11.009〉
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Etienne Morel, Sara Ghezzal, Geraldine 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, Elsevier, 2018, 1863 (2), pp.199-211. 〈http://www.sciencedirect.com/science/article/pii/S1388198117302330〉. 〈10.1016/j.bbalip.2017.11.009〉. 〈hal-01661856〉

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