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Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling

Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin family with diverse functions in epithelial cells, including cell migration, cell contact maturation, and tight junction formation. In endothelial cells, JAM-A has been implicated in basic fibroblast growth factor (bFGF)-regula...

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Autores principales: Peddibhotla, Swetha S. D., Brinkmann, Benjamin F., Kummer, Daniel, Tuncay, Hüseyin, Nakayama, Masanori, Adams, Ralf H., Gerke, Volker, Ebnet, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608503/
https://www.ncbi.nlm.nih.gov/pubmed/23389628
http://dx.doi.org/10.1091/mbc.E12-06-0481
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author Peddibhotla, Swetha S. D.
Brinkmann, Benjamin F.
Kummer, Daniel
Tuncay, Hüseyin
Nakayama, Masanori
Adams, Ralf H.
Gerke, Volker
Ebnet, Klaus
author_facet Peddibhotla, Swetha S. D.
Brinkmann, Benjamin F.
Kummer, Daniel
Tuncay, Hüseyin
Nakayama, Masanori
Adams, Ralf H.
Gerke, Volker
Ebnet, Klaus
author_sort Peddibhotla, Swetha S. D.
collection PubMed
description Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin family with diverse functions in epithelial cells, including cell migration, cell contact maturation, and tight junction formation. In endothelial cells, JAM-A has been implicated in basic fibroblast growth factor (bFGF)-regulated angiogenesis through incompletely understood mechanisms. In this paper, we identify tetraspanin CD9 as novel binding partner for JAM-A in endothelial cells. CD9 acts as scaffold and assembles a ternary JAM-A-CD9-αvβ3 integrin complex from which JAM-A is released upon bFGF stimulation. CD9 interacts predominantly with monomeric JAM-A, which suggests that bFGF induces signaling by triggering JAM-A dimerization. Among the two vitronectin receptors, αvβ3 and αvβ5 integrin, which have been shown to cooperate during angiogenic signaling with bFGF and vascular endothelial growth factor (VEGF), respectively, CD9 links JAM-A specifically to αvβ3 integrin. In line with this, knockdown of CD9 blocks bFGF- but not VEGF-induced ERK1/2 activation. JAM-A or CD9 knockdown impairs endothelial cell migration and tube formation. Our findings indicate that CD9 incorporates monomeric JAM-A into a complex with αvβ3 integrin, which responds to bFGF stimulation by JAM-A release to regulate mitogen-activated protein kinase (MAPK) activation, endothelial cell migration, and angiogenesis. The data also provide new mechanistic insights into the cooperativity between bFGF and αvβ3 integrin during angiogenic signaling.
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spelling pubmed-36085032013-06-16 Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling Peddibhotla, Swetha S. D. Brinkmann, Benjamin F. Kummer, Daniel Tuncay, Hüseyin Nakayama, Masanori Adams, Ralf H. Gerke, Volker Ebnet, Klaus Mol Biol Cell Articles Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin family with diverse functions in epithelial cells, including cell migration, cell contact maturation, and tight junction formation. In endothelial cells, JAM-A has been implicated in basic fibroblast growth factor (bFGF)-regulated angiogenesis through incompletely understood mechanisms. In this paper, we identify tetraspanin CD9 as novel binding partner for JAM-A in endothelial cells. CD9 acts as scaffold and assembles a ternary JAM-A-CD9-αvβ3 integrin complex from which JAM-A is released upon bFGF stimulation. CD9 interacts predominantly with monomeric JAM-A, which suggests that bFGF induces signaling by triggering JAM-A dimerization. Among the two vitronectin receptors, αvβ3 and αvβ5 integrin, which have been shown to cooperate during angiogenic signaling with bFGF and vascular endothelial growth factor (VEGF), respectively, CD9 links JAM-A specifically to αvβ3 integrin. In line with this, knockdown of CD9 blocks bFGF- but not VEGF-induced ERK1/2 activation. JAM-A or CD9 knockdown impairs endothelial cell migration and tube formation. Our findings indicate that CD9 incorporates monomeric JAM-A into a complex with αvβ3 integrin, which responds to bFGF stimulation by JAM-A release to regulate mitogen-activated protein kinase (MAPK) activation, endothelial cell migration, and angiogenesis. The data also provide new mechanistic insights into the cooperativity between bFGF and αvβ3 integrin during angiogenic signaling. The American Society for Cell Biology 2013-04-01 /pmc/articles/PMC3608503/ /pubmed/23389628 http://dx.doi.org/10.1091/mbc.E12-06-0481 Text en © 2013 Peddibhotla et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Peddibhotla, Swetha S. D.
Brinkmann, Benjamin F.
Kummer, Daniel
Tuncay, Hüseyin
Nakayama, Masanori
Adams, Ralf H.
Gerke, Volker
Ebnet, Klaus
Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling
title Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling
title_full Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling
title_fullStr Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling
title_full_unstemmed Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling
title_short Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling
title_sort tetraspanin cd9 links junctional adhesion molecule-a to αvβ3 integrin to mediate basic fibroblast growth factor–specific angiogenic signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608503/
https://www.ncbi.nlm.nih.gov/pubmed/23389628
http://dx.doi.org/10.1091/mbc.E12-06-0481
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