TY - JOUR
T1 - Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1
AU - Kagawa, Yoshiteru
AU - Yasumoto, Yuki
AU - Sharifi, Kazem
AU - Ebrahimi, Majid
AU - Islam, Ariful
AU - Miyazaki, Hirofumi
AU - Yamamoto, Yui
AU - Sawada, Tomoo
AU - Kishi, Hiroko
AU - Kobayashi, Sei
AU - Maekawa, Motoko
AU - Yoshikawa, Takeo
AU - Takaki, Eiichi
AU - Nakai, Akira
AU - Kogo, Hiroshi
AU - Fujimoto, Toyoshi
AU - Owada, Yuji
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Caveolin-1
KW - Fatty acid binding protein
KW - Lipid raft
KW - Signal transduction
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U2 - 10.1002/glia.22784
DO - 10.1002/glia.22784
M3 - Article
C2 - 25601031
AN - SCOPUS:84925272227
VL - 63
SP - 780
EP - 794
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 5
ER -