1. Academic Validation
  2. Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier

Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier

  • Sci Adv. 2020 May 29;6(22):eaay8627. doi: 10.1126/sciadv.aay8627.
Zhifu Wang 1 2 Yongtao Zheng 1 Fan Wang 1 3 Junjie Zhong 1 Tong Zhao 1 Qiang Xie 1 Tongming Zhu 1 Fukai Ma 1 Qisheng Tang 1 Bin Zhou 2 Jianhong Zhu 1
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Huashan Hospital, Institute of Brain Science, State Key laboratory of Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, Shanghai Medical College, Fudan University, No.12 Urumqi Mid Road, Shanghai 200040, China.
  • 2 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), University of CAS, Shanghai, China.
  • 3 Department of Neurology, Peking University Third Hospital, Beijing, China.
Abstract

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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