title: JAM-L-mediated leukocyte adhesion to endothelial cells is regulated in cis by alpha4beta1 integrin activation.
abstract: 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.
authors.affiliation: Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris F-75014, France.
authors.forename: Anny-Claude
authors.initials: AC
authors.lastname: Luissint
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Lutz
authors.forename: David A
authors.initials: DA
authors.lastname: Calderwood
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bourdoulous
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D019281:Dimerization; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: C568771:CLMP protein, human; D015815:Cell Adhesion Molecules; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D039041:Integrin alpha4beta1; C479820:JAML protein, human; D011991:Receptors, Virus