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

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 i...

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Autores principales: Wang, Zhifu, Zheng, Yongtao, Wang, Fan, Zhong, Junjie, Zhao, Tong, Xie, Qiang, Zhu, Tongming, Ma, Fukai, Tang, Qisheng, Zhou, Bin, Zhu, Jianhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259944/
https://www.ncbi.nlm.nih.gov/pubmed/32523984
http://dx.doi.org/10.1126/sciadv.aay8627
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author Wang, Zhifu
Zheng, Yongtao
Wang, Fan
Zhong, Junjie
Zhao, Tong
Xie, Qiang
Zhu, Tongming
Ma, Fukai
Tang, Qisheng
Zhou, Bin
Zhu, Jianhong
author_facet Wang, Zhifu
Zheng, Yongtao
Wang, Fan
Zhong, Junjie
Zhao, Tong
Xie, Qiang
Zhu, Tongming
Ma, Fukai
Tang, Qisheng
Zhou, Bin
Zhu, Jianhong
author_sort Wang, Zhifu
collection PubMed
description 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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spelling pubmed-72599442020-06-09 Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier Wang, Zhifu Zheng, Yongtao Wang, Fan Zhong, Junjie Zhao, Tong Xie, Qiang Zhu, Tongming Ma, Fukai Tang, Qisheng Zhou, Bin Zhu, Jianhong Sci Adv Research Articles 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. American Association for the Advancement of Science 2020-05-29 /pmc/articles/PMC7259944/ /pubmed/32523984 http://dx.doi.org/10.1126/sciadv.aay8627 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Wang, Zhifu
Zheng, Yongtao
Wang, Fan
Zhong, Junjie
Zhao, Tong
Xie, Qiang
Zhu, Tongming
Ma, Fukai
Tang, Qisheng
Zhou, Bin
Zhu, Jianhong
Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier
title Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier
title_full Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier
title_fullStr Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier
title_full_unstemmed Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier
title_short Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier
title_sort mfsd2a and spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259944/
https://www.ncbi.nlm.nih.gov/pubmed/32523984
http://dx.doi.org/10.1126/sciadv.aay8627
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