Abstract
How plasma membrane (PM) cholesterol is controlled is poorly understood. Ablation of the gene encoding the ER stress steroidogenic acute regulatory-related lipid transfer domain (StarD)5 leads to a decrease in PM cholesterol content, a decrease in cholesterol efflux, and an increase in intracellular neutral lipid accumulation in macrophages, the major cell type that expresses StarD5. ER stress increases StarD5 expression in mouse hepatocytes, which results in an increase in accessible PM cholesterol in WT but not in StarD5-/- hepatocytes. StarD5-/- mice store higher levels of cholesterol and triglycerides, which leads to altered expression of cholesterol-regulated genes. In vitro, a recombinant GST-StarD5 protein transfers cholesterol between synthetic liposomes. StarD5 overexpression leads to a marked increase in PM cholesterol. Phasor analysis of 6-dodecanoyl-2-dimethylaminonaphthalene fluorescence lifetime imaging microscopy data revealed an increase in PM fluidity in StarD5-/- macrophages. Taken together, these studies show that StarD5 is a stress-responsive protein that regulates PM cholesterol and intracellular cholesterol homeostasis.
Highlights
How plasma membrane (PM) cholesterol is controlled is poorly understood
Within the PM, cholesterol plays an essential role in regulating fluidity, lipid raft structure, cell signaling, and Abbreviations: CHOP, CCAAT-enhancer-binding protein homologous; FACS, fluorescence activated cell sorting; fALOD4, fluorescence anthrolysin O domain 4; Fluorescence lifetime imaging microscopy (FLIM), fluorescence lifetime imaging microscopy; LAURDAN, 6-dodecanoyl-2-dimethylaminonaphthalene; Multiplicity of infection (MOI), multiplicity of infection; NiemannPick C (NPC), Niemann-Pick C; OSBP, oxysterol-binding protein; PM, plasma membrane; PNS, post-nuclear supernatant; qRT-PCR, quantitative RT-PCR; ssODN, single-stranded oligodeoxynucleotide; StarD, steroidogenic acute regulatory-related lipid transfer domain; START, steroidogenic acute regulatory protein-related lipid transfer; Tg, thapsigargin; VCU, Virginia Commonwealth University
It has been proposed that NPC1 mediates the exit of LDL-derived cholesterol from lysosomes to the ER [23, 52], recent studies suggest that NPC1 mediates the exit of cholesterol from the lysosomes to the PM [3, 12]
Summary
How plasma membrane (PM) cholesterol is controlled is poorly understood. Ablation of the gene encoding the ER stress steroidogenic acute regulatory-related lipid transfer domain (StarD) leads to a decrease in PM cholesterol content, a decrease in cholesterol efflux, and an increase in intracellular neutral lipid accumulation in macrophages, the major cell type that expresses StarD5. Phasor analysis of 6-dodecanoyl-2-dimethylaminonaphthalene fluorescence lifetime imaging microscopy data revealed an increase in PM fluidity in StarD5 / macrophages Taken together, these studies show that StarD5 is a stress-responsive protein that regulates PM cholesterol and intracellular cholesterol homeostasis.— Rodriguez-Agudo, D., L. Within the PM, cholesterol plays an essential role in regulating fluidity, lipid raft structure, cell signaling, and Abbreviations: CHOP, CCAAT-enhancer-binding protein homologous; FACS, fluorescence activated cell sorting; fALOD4, fluorescence anthrolysin O domain 4; FLIM, fluorescence lifetime imaging microscopy; LAURDAN, 6-dodecanoyl-2-dimethylaminonaphthalene; MOI, multiplicity of infection; NPC, Niemann-Pick C; OSBP, oxysterol-binding protein; PM, plasma membrane; PNS, post-nuclear supernatant; qRT-PCR, quantitative RT-PCR; ssODN, single-stranded oligodeoxynucleotide; StarD, steroidogenic acute regulatory-related lipid transfer domain; START, steroidogenic acute regulatory protein-related lipid transfer; Tg, thapsigargin; VCU, Virginia Commonwealth University
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
