StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis
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...
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doaj-b9c9fc18d2e84c2ebc2b6623be3dd2112021-04-29T04:35:19ZengElsevierJournal of Lipid Research0022-22752019-06-0160610871098StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasisDaniel Rodriguez-Agudo0Leonel Malacrida1Genta Kakiyama2Tavis Sparrer3Carolina Fortes4Michael Maceyka5Mark A. Subler6Jolene J. Windle7Enrico Gratton8William M. Pandak9Gregorio Gil10Departments of Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298; McGuire Veterans Affairs Medical Center, Richmond, VA 23248Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California at Irvine, Irvine, CA 92697; Area de Investigación Respiratoria, Departamento de Fisiopatologia, Hospital de Clinicas, Facultad de Medicina, Universidad de la Republica, Montevideo, UruguayDepartments of Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298; McGuire Veterans Affairs Medical Center, Richmond, VA 23248Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298Departments of Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298; Departmento de Biologia Molecular y Bioquimica, Universidad de Malaga, Malaga, SpainBiochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298; Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298; Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California at Irvine, Irvine, CA 92697To whom correspondence should be addressed; Departments of Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298; McGuire Veterans Affairs Medical Center, Richmond, VA 23248To whom correspondence should be addressed; Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298; Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298How 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.http://www.sciencedirect.com/science/article/pii/S0022227520322495cholesterol traffickingmacrophagesendoplasmic reticulumNiemann-Pick Cfluorescencesteroidogenic acute regulatory protein-related lipid transfer proteins |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniel Rodriguez-Agudo Leonel Malacrida Genta Kakiyama Tavis Sparrer Carolina Fortes Michael Maceyka Mark A. Subler Jolene J. Windle Enrico Gratton William M. Pandak Gregorio Gil |
spellingShingle |
Daniel Rodriguez-Agudo Leonel Malacrida Genta Kakiyama Tavis Sparrer Carolina Fortes Michael Maceyka Mark A. Subler Jolene J. Windle Enrico Gratton William M. Pandak Gregorio Gil StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis Journal of Lipid Research cholesterol trafficking macrophages endoplasmic reticulum Niemann-Pick C fluorescence steroidogenic acute regulatory protein-related lipid transfer proteins |
author_facet |
Daniel Rodriguez-Agudo Leonel Malacrida Genta Kakiyama Tavis Sparrer Carolina Fortes Michael Maceyka Mark A. Subler Jolene J. Windle Enrico Gratton William M. Pandak Gregorio Gil |
author_sort |
Daniel Rodriguez-Agudo |
title |
StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis |
title_short |
StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis |
title_full |
StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis |
title_fullStr |
StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis |
title_full_unstemmed |
StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis |
title_sort |
stard5: an er stress protein regulates plasma membrane and intracellular cholesterol homeostasis |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2019-06-01 |
description |
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. |
topic |
cholesterol trafficking macrophages endoplasmic reticulum Niemann-Pick C fluorescence steroidogenic acute regulatory protein-related lipid transfer proteins |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520322495 |
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