Physical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase—Novel Cell Adhesion in Neural Stem cell Vascular Niche
Abstract Brain neural stem cells and transit amplifying cells in the subventricular zone (SVZ) of the lateral ventricles are in direct contact with the microvascular endothelium. The mechanisms/molecules of direct cell contact in the SVZ neurovascular niche are not fully understood. We previously sh...
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2017
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oai:doaj.org-article:ac19b7711d544673a880389e0d22e7602021-12-02T11:52:23ZPhysical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase—Novel Cell Adhesion in Neural Stem cell Vascular Niche10.1038/s41598-017-05131-42045-2322https://doaj.org/article/ac19b7711d544673a880389e0d22e7602017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05131-4https://doaj.org/toc/2045-2322Abstract Brain neural stem cells and transit amplifying cells in the subventricular zone (SVZ) of the lateral ventricles are in direct contact with the microvascular endothelium. The mechanisms/molecules of direct cell contact in the SVZ neurovascular niche are not fully understood. We previously showed that neural stem/progenitor (NS/P) cells induce brain endothelial signaling in direct cell contact through matriptase (MTP) on NS/P cell surface. In the present study, using pull-down and LC-MS/MS, we identified melanoma cell adhesion molecule (MCAM) the brain endothelial molecule that interacts with MTP. MCAM physically binds to the CUB domains of MTP and induces a chain of brain endothelial signaling including p38MAPK activation, GSK3β inactivation and subsequently β-catenin activation; none of these signaling events occurred when either MTP or MCAM is deleted. MTP-MCAM binding and induction of endothelial signaling were all sensitive to cholera toxin. Together, we identified key molecules that may represent a mechanism in neural stem cell vascular niche regulation.Hsiu-Hui TungSheau-Ling LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q Hsiu-Hui Tung Sheau-Ling Lee Physical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase—Novel Cell Adhesion in Neural Stem cell Vascular Niche |
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Abstract Brain neural stem cells and transit amplifying cells in the subventricular zone (SVZ) of the lateral ventricles are in direct contact with the microvascular endothelium. The mechanisms/molecules of direct cell contact in the SVZ neurovascular niche are not fully understood. We previously showed that neural stem/progenitor (NS/P) cells induce brain endothelial signaling in direct cell contact through matriptase (MTP) on NS/P cell surface. In the present study, using pull-down and LC-MS/MS, we identified melanoma cell adhesion molecule (MCAM) the brain endothelial molecule that interacts with MTP. MCAM physically binds to the CUB domains of MTP and induces a chain of brain endothelial signaling including p38MAPK activation, GSK3β inactivation and subsequently β-catenin activation; none of these signaling events occurred when either MTP or MCAM is deleted. MTP-MCAM binding and induction of endothelial signaling were all sensitive to cholera toxin. Together, we identified key molecules that may represent a mechanism in neural stem cell vascular niche regulation. |
format |
article |
author |
Hsiu-Hui Tung Sheau-Ling Lee |
author_facet |
Hsiu-Hui Tung Sheau-Ling Lee |
author_sort |
Hsiu-Hui Tung |
title |
Physical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase—Novel Cell Adhesion in Neural Stem cell Vascular Niche |
title_short |
Physical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase—Novel Cell Adhesion in Neural Stem cell Vascular Niche |
title_full |
Physical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase—Novel Cell Adhesion in Neural Stem cell Vascular Niche |
title_fullStr |
Physical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase—Novel Cell Adhesion in Neural Stem cell Vascular Niche |
title_full_unstemmed |
Physical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase—Novel Cell Adhesion in Neural Stem cell Vascular Niche |
title_sort |
physical binding of endothelial mcam and neural transmembrane protease matriptase—novel cell adhesion in neural stem cell vascular niche |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/ac19b7711d544673a880389e0d22e760 |
work_keys_str_mv |
AT hsiuhuitung physicalbindingofendothelialmcamandneuraltransmembraneproteasematriptasenovelcelladhesioninneuralstemcellvascularniche AT sheaulinglee physicalbindingofendothelialmcamandneuraltransmembraneproteasematriptasenovelcelladhesioninneuralstemcellvascularniche |
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1718395062540304384 |