Dual interaction of JAM-C with JAM-B and alpha(M)beta2 integrin: function in junctional complexes and leukocyte adhesion.
The junctional adhesion molecules (JAMs) have been recently described as interendothelial junctional molecules and as integrin ligands. Here we show that JAM-B and JAM-C undergo heterophilic interaction in cell-cell contacts and that JAM-C is recruited and stabilized in junctional complexes by JAM-B. In addition, soluble JAM-B dissociates soluble JAM-C homodimers to form JAM-B/JAM-C heterodimers. This suggests that the affinity of JAM-C monomers to form dimers is higher for JAM-B than for JAM-C. Using antibodies against JAM-C, the formation of JAM-B/JAM-C heterodimers can be abolished. This liberates JAM-C from its vascular binding partner JAM-B and makes it available on the apical side of vessels for interaction with its leukocyte counter-receptor alpha(M)beta2 integrin. We demonstrate that the modulation of JAM-C localization in junctional complexes is a new regulatory mechanism for alpha(M)beta2-dependent adhesion of leukocytes.
Lamagna
Chrystelle
C
Department of Pathology and Immunology, Centre Médical Universitaire, 1204 Geneva, Switzerland.
Meda
Paolo
P
Mandicourt
Guillaume
G
Brown
James
J
Gilbert
Robert J C
RJ
Jones
E Yvonne
EY
Kiefer
Friedemann
F
Ruga
Pilar
P
Imhof
Beat A
BA
Aurrand-Lions
Michel
M
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018920:Coculture Techniques; D006224:Cricetinae; D003412:Cricetulus; D004727:Endothelium / Q000502:physiology / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007365:Intercellular Junctions / Q000502:physiology* / Q000648:ultrastructure; D007962:Leukocytes / Q000502:physiology* / Q000648:ultrastructure; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016177:Macrophage-1 Antigen; D009842:Oligopeptides; D010455:Peptides; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C085706:FLAG peptide