血脑屏障
主要促进者超家族
1-磷酸鞘氨醇
细胞生物学
鞘氨醇
中枢神经系统
机制(生物学)
平衡
化学
神经科学
生物
运输机
生物化学
受体
基因
认识论
哲学
作者
Zhifu Wang,Yonggui Zheng,Fan Wang,Junjie Zhong,Tingting Zhao,Qiang Xie,Tongming Zhu,Fukai Ma,Qisheng Tang,Bin Zhou,Jianhong Zhu
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2020-05-29
卷期号:6 (22)
被引量:29
标识
DOI:10.1126/sciadv.aay8627
摘要
To maintain brain homeostasis, a unique interface known as the blood-brain barrier (BBB) is formed between the blood circulation and the central nervous system (CNS). Major facilitator superfamily domain-containing 2a (Mfsd2a) is a specific marker of the BBB. However, the mechanism by which Mfsd2a influences the BBB is poorly understood. In this study, we demonstrated that Mfsd2a is essential for sphingosine-1-phosphate (S1P) export from endothelial cells in the brain. We found that Mfsd2a and Spinster homolog 2 (Spns2) form a protein complex to ensure the efficient transport of S1P. Furthermore, the S1P-rich microenvironment in the extracellular matrix (ECM) in the vascular endothelium dominates the formation and maintenance of the BBB. We demonstrated that different concentrations of S1P have different effects on BBB integrity. These findings help to unravel the mechanism by which S1P regulates BBB and also provide previously unidentified insights into the delivery of neurological drugs in the CNS.
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