Document Detail


Neural transmembrane protease and endothelial Gs protein activation in cell contact-dependent signaling between neural stem/progenitor cells and brain endothelial cells.
MedLine Citation:
PMID:  22577149     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vasculature is an important component of the neural stem cell niche in brain. It regulates neural stem/progenitor (NS/P) cell self-renewal, differentiation, and migration. In the neurogenic niches of adult brain, NS/P cells lie close to blood vessels, and proliferating NS/P cells frequently contact the vasculature. In the present study we showed that NS/P cells in co-culture with brain endothelial (bEND) cells activated endothelial G proteins and p38 mitogen-activated protein kinase (p38 MAPK) and stimulated cytokine/chemokine expression. These NS/P cell-induced endothelial responses took place during NS/P cell and bEND cell direct contact and were critically dependent on the expression of the type II transmembrane serine protease matriptase (MTP) by NS/P cells, because knocking down of MTP in NS/P cells impaired and re-expression of MTP restored their ability to induce endothelial cytokine/chemokine expression, p38 MAPK, or G protein activation. Cholera toxin blocked NS/P cell-induced endothelial responses, suggesting that the endothelial G protein activated by NS/P MTP is in the G(s) subfamily. The addition of p38 MAPK inhibitor impaired NS/P cell-induced endothelial cytokine/chemokine expression. The known G protein-coupled receptor substrate of MTP, protease-activated receptor 2, was not involved in this system. These results revealed a novel signaling pathway in neural stem cell vascular niches that is mediated by neural MTP and endothelial G(s) protein signaling at the cell-cell interface. This is the first report of direct cell-cell signaling between NS/P and bEND cells.
Authors:
Hsiu-Hui Tung; Sheau-Ling Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-10
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-09-11     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22497-508     Citation Subset:  IM    
Affiliation:
Institute of Cellular and Systems Medicine, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan, Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / blood supply,  cytology
Cell Communication / physiology*
Cell Differentiation / drug effects,  physiology
Cell Movement / physiology
Cells, Cultured
Chemokines / metabolism
Coculture Techniques
Culture Media, Conditioned / pharmacology
Cytokines / metabolism
Endothelial Cells / cytology*,  metabolism*
Ependyma / blood supply,  cytology
GTP-Binding Protein alpha Subunits, Gs / metabolism
GTP-Binding Proteins / metabolism
Green Fluorescent Proteins / genetics
Interleukin-6 / pharmacology
MAP Kinase Signaling System / physiology
Male
Mice
Mice, Inbred Strains
Mice, Mutant Strains
Neural Stem Cells / cytology*,  metabolism*
Stem Cell Niche / physiology
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Chemokines; 0/Culture Media, Conditioned; 0/Cytokines; 0/Interleukin-6; 147336-22-9/Green Fluorescent Proteins; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.6.1.-/GTP-Binding Proteins; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gs

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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