JAM-L-mediated leukocyte adhesion to endothelial cells is regulated in cis by alpha4beta1 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 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.
Luissint
Anny-Claude
AC
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris F-75014, France.
Lutz
Pierre G
PG
Calderwood
David A
DA
Couraud
Pierre-Olivier
PO
Bourdoulous
Sandrine
S
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
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