Fatty Acid-Binding Protein 7 Regulates Function of Caveolae in Astrocytes through Expression of Caveolin-1
Fatty Acid-Binding Protein 7 Regulates Function of Caveolae in Astrocytes through Expression of Caveolin-1
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DOI：
10.1002/glia.22784
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发表时间：
2015-05-01
期刊：
影响因子：
6.2
通讯作者：
Owada，Yuji
中科院分区：
文献类型：
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作者：
Kagawa，Yoshiteru;Yasumoto，Yuki;Owada，Yuji
脂肪酸结合蛋白（FABP）结合并溶解长链脂肪酸，控制细胞内脂质动态。 FABP7 由发育中的大脑中的星形胶质细胞表达，并被认为参与星形胶质细胞脂质稳态的控制。在本研究中，我们试图检查 FABP7 在星形胶质细胞中的作用，重点关注质膜脂筏功能，这对于响应细胞外刺激的受体介导的信号转导非常重要。与野生型星形胶质细胞相比，在FABP7敲除（KO）星形胶质细胞中，脂多糖（LPS）刺激后，Toll样受体4（TLR4）和神经胶质细胞源性神经营养因子受体α1在脂筏中的配体依赖性积累减少，丝裂原激活蛋白激酶和核因子κB的活化受损。此外，发现caveolin-1（而不是cavin-1、2、3、caveolin-2和flotillin-1）的表达在蛋白质和转录水平上降低。 FABP7-KO 星形胶质细胞中 FABP7 的重新表达挽救了 Caveolin-1 水平的下降。此外，caveolin-1转染FABP7-KO星形胶质细胞显着增加了脂筏中TLR4的募集以及LPS刺激后肿瘤坏死因子-α的产生。综上所述，这些数据表明 FABP7 通过调节 Caveolin-1 的表达来控制脂筏功能，并参与星形胶质细胞对外部刺激的反应。 GLIA 2015；63：780–794
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