TY - JOUR
T1 - Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells
AU - Morel, Etienne
AU - Ghezzal, Sara
AU - Lucchi, Géraldine
AU - Truntzer, Caroline
AU - Pais de Barros, Jean Paul
AU - Simon-Plas, Françoise
AU - Demignot, Sylvie
AU - Mineo, Chieko
AU - Shaul, Philip W.
AU - Leturque, Armelle
AU - Rousset, Monique
AU - Carrière, Véronique
N1 - Funding Information:
This research was supported by Institut National de la Santé et de la Recherche Médicale ( INSERM ) and Université Pierre et Marie Curie (Paris 6) ( UMRS1138 ), and also by National Institutes of Health grants R01-HL131597 (P.W.S.) and R01-HL126795 (C.M.).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/2
Y1 - 2018/2
N2 - 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.
AB - 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.
KW - Cholesterol
KW - Lipid raft
KW - Lipid trafficking
KW - Scavenger receptor
KW - Sphingolipid
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U2 - 10.1016/j.bbalip.2017.11.009
DO - 10.1016/j.bbalip.2017.11.009
M3 - Article
C2 - 29196159
AN - SCOPUS:85044727955
SN - 1388-1981
VL - 1863
SP - 199
EP - 211
JO - BBA - Specialised Section On Lipids and Related Subjects
JF - BBA - Specialised Section On Lipids and Related Subjects
IS - 2
ER -