title: Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1.
abstract: Fatty acid-binding proteins (FABPs) bind and solubilize long-chain fatty acids, controlling intracellular lipid dynamics. FABP7 is expressed by astrocytes in the developing brain, and suggested to be involved in the control of astrocyte lipid homeostasis. In this study, we sought to examine the role of FABP7 in astrocytes, focusing on plasma membrane lipid raft function, which is important for receptor-mediated signal transduction in response to extracellular stimuli. In FABP7-knockout (KO) astrocytes, the ligand-dependent accumulation of Toll-like receptor 4 (TLR4) and glial cell-line-derived neurotrophic factor receptor alpha 1 into lipid raft was decreased, and the activation of mitogen-activated protein kinases and nuclear factor-κB was impaired after lipopolysaccharide (LPS) stimulation when compared with wild-type astrocytes. In addition, the expression of caveolin-1, not cavin-1, 2, 3, caveolin-2, and flotillin-1, was found to be decreased at the protein and transcriptional levels. FABP7 re-expression in FABP7-KO astrocytes rescued the decreased level of caveolin-1. Furthermore, caveolin-1-transfection into FABP7-KO astrocytes significantly increased TLR4 recruitment into lipid raft and tumor necrosis factor-α production after LPS stimulation. Taken together, these data suggest that FABP7 controls lipid raft function through the regulation of caveolin-1 expression and is involved in the response of astrocytes to the external stimuli. GLIA 2015;63:780-794.
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yasumoto
authors.forename: Kazem
authors.initials: K
authors.lastname: Sharifi
authors.forename: Majid
authors.initials: M
authors.lastname: Ebrahimi
authors.forename: Ariful
authors.initials: A
authors.lastname: Islam
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Tomoo
authors.initials: T
authors.lastname: Sawada
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kishi
authors.forename: Sei
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Motoko
authors.initials: M
authors.lastname: Maekawa
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Takaki
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kogo
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D051242:Caveolin 1; D016207:Cytokines; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D002784:Cholesterol
keywords: astrocytes; caveolin-1; fatty acid binding protein; lipid raft; signal transduction