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 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, GSK3? inactivation and subsequently ?-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.

SUBMITTER: Tung HH 

PROVIDER: S-EPMC5504030 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature