Cargando…

JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation

Junctional adhesion molecules (JAMs) are endothelial and epithelial adhesion molecules involved in the recruitment of circulating leukocytes to inflammatory sites. We show here that JAM-L, a protein related to the JAM family, is restricted to leukocytes and promotes their adhesion to endothelial cel...

Descripción completa

Detalles Bibliográficos
Autores principales: Luissint, Anny-Claude, Lutz, Pierre G., Calderwood, David A., Couraud, Pierre-Olivier, Bourdoulous, Sandrine
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600739/
https://www.ncbi.nlm.nih.gov/pubmed/19064666
http://dx.doi.org/10.1083/jcb.200805061
_version_ 1782162203370061824
author Luissint, Anny-Claude
Lutz, Pierre G.
Calderwood, David A.
Couraud, Pierre-Olivier
Bourdoulous, Sandrine
author_facet Luissint, Anny-Claude
Lutz, Pierre G.
Calderwood, David A.
Couraud, Pierre-Olivier
Bourdoulous, Sandrine
author_sort Luissint, Anny-Claude
collection PubMed
description Junctional adhesion molecules (JAMs) are endothelial and epithelial adhesion molecules involved in the recruitment of circulating leukocytes to inflammatory sites. We show here that JAM-L, a protein related to the JAM family, is restricted to leukocytes and promotes their adhesion to endothelial cells. Cis dimerization of JAM-L is required to engage in heterophilic interactions with its cognate counter-receptor CAR (coxsackie and adenovirus receptor). Interestingly, JAM-L expressed on neutrophils binds CAR independently of integrin activation. However, on resting monocytes and T lymphocytes, which express the integrin VLA-4, JAM-L molecules engage in complexes with VLA-4 and mainly accumulate in their monomeric form. Integrin activation is required for the dissociation of JAM-L–VLA-4 complexes and the accumulation of functional JAM-L dimers, which indicates that the leukocyte integrin VLA-4 controls JAM-L function in cis by controlling its dimerization state. This provides a mechanism through which VLA-4 and JAM-L functions are coordinately regulated, allowing JAM-L to strengthen integrin-dependent adhesion of leukocytes to endothelial cells.
format Text
id pubmed-2600739
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-26007392009-06-15 JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation Luissint, Anny-Claude Lutz, Pierre G. Calderwood, David A. Couraud, Pierre-Olivier Bourdoulous, Sandrine J Cell Biol Research Articles Junctional adhesion molecules (JAMs) are endothelial and epithelial adhesion molecules involved in the recruitment of circulating leukocytes to inflammatory sites. We show here that JAM-L, a protein related to the JAM family, is restricted to leukocytes and promotes their adhesion to endothelial cells. Cis dimerization of JAM-L is required to engage in heterophilic interactions with its cognate counter-receptor CAR (coxsackie and adenovirus receptor). Interestingly, JAM-L expressed on neutrophils binds CAR independently of integrin activation. However, on resting monocytes and T lymphocytes, which express the integrin VLA-4, JAM-L molecules engage in complexes with VLA-4 and mainly accumulate in their monomeric form. Integrin activation is required for the dissociation of JAM-L–VLA-4 complexes and the accumulation of functional JAM-L dimers, which indicates that the leukocyte integrin VLA-4 controls JAM-L function in cis by controlling its dimerization state. This provides a mechanism through which VLA-4 and JAM-L functions are coordinately regulated, allowing JAM-L to strengthen integrin-dependent adhesion of leukocytes to endothelial cells. The Rockefeller University Press 2008-12-15 /pmc/articles/PMC2600739/ /pubmed/19064666 http://dx.doi.org/10.1083/jcb.200805061 Text en © 2008 Luissint et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Luissint, Anny-Claude
Lutz, Pierre G.
Calderwood, David A.
Couraud, Pierre-Olivier
Bourdoulous, Sandrine
JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation
title JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation
title_full JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation
title_fullStr JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation
title_full_unstemmed JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation
title_short JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation
title_sort jam-l–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600739/
https://www.ncbi.nlm.nih.gov/pubmed/19064666
http://dx.doi.org/10.1083/jcb.200805061
work_keys_str_mv AT luissintannyclaude jamlmediatedleukocyteadhesiontoendothelialcellsisregulatedincisbya4b1integrinactivation
AT lutzpierreg jamlmediatedleukocyteadhesiontoendothelialcellsisregulatedincisbya4b1integrinactivation
AT calderwooddavida jamlmediatedleukocyteadhesiontoendothelialcellsisregulatedincisbya4b1integrinactivation
AT couraudpierreolivier jamlmediatedleukocyteadhesiontoendothelialcellsisregulatedincisbya4b1integrinactivation
AT bourdouloussandrine jamlmediatedleukocyteadhesiontoendothelialcellsisregulatedincisbya4b1integrinactivation