Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis.
Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis.
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DOI：
10.1016/j.neuron.2017.03.043
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发表时间：
2017-05-03
期刊：
影响因子：
16.2
通讯作者：
Gu C
中科院分区：
文献类型：
--
作者：
Andreone BJ;Chow BW;Tata A;Lacoste B;Ben-Zvi A;Bullock K;Deik AA;Ginty DD;Clish CB;Gu C
血脑屏障（BBB）提供了一个恒定的稳态脑环境，这是必要的适当的神经功能。相对于外周内皮细胞，异常低的囊泡转运率（胞吞转运）已被确定为维持BBB限制性质量的中枢神经系统（CNS）内皮细胞的两个独特特性之一。然而，尚不清楚这种低转胞吞率是如何实现的。在这里，我们提供了一种机制，中枢神经系统内皮细胞脂质成分的调节抑制特异性小窝介导的转胞途径容易在外周使用。无偏的脂质组学分析揭示了CNS和外周的内皮细胞脂质特征的显著差异，这是脑内皮细胞中小窝囊泡形成和运输抑制的基础。此外，由Mfsd2a转运的脂质建立了独特的脂质环境，其抑制CNS内皮细胞中的小窝囊泡形成以抑制胞吞转运并确保BBB完整性。
The blood-brain barrier (BBB) provides a constant homeostatic brain environment that is essential for proper neural function. An unusually low rate of vesicular transport (transcytosis) has been identified as one of the two unique properties of central nervous system (CNS) endothelial cells, relative to peripheral endothelial cells, that maintain the restrictive quality of the BBB. However, it is not known how this low rate of transcytosis is achieved. Here we provide a mechanism whereby the regulation of CNS endothelial cell lipid composition inhibits specifically the caveolae-mediated transcytotic route readily used in the periphery. An unbiased lipidomic analysis reveals significant differences in endothelial cell lipid signatures from the CNS and periphery, which underlie a suppression of caveolae vesicle formation and trafficking in brain endothelial cells. Furthermore, lipids transported by Mfsd2a establish a unique lipid environment that inhibits caveolae vesicle formation in CNS endothelial cells to suppress transcytosis and ensure BBB integrity.