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Vol. 16, Issue 10, 4992-5003, October 2005
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M
2 Integrin: Function in Junctional Complexes and Leukocyte Adhesion
* Departments of Pathology and Immunology, Centre Médical Universitaire, 1204 Geneva, Switzerland;
Departments of Cell Physiology and Metabolism, Centre Médical Universitaire, 1204 Geneva, Switzerland;
Division of Structural Biology, Henry Wellcome Building of Genomic Medicine, Headington, Oxford OX3 7BN, United Kingdom;
Cancer Research UK Receptor Structure Group, Henry Wellcome Building of Genomic Medicine, Headington, Oxford OX3 7BN, United Kingdom; and
|| Max-Planck-Institute for Molecular Biomedicine, Institute for Vascular Cell Biology, D-48149 Münster, Germany
Submitted April 13, 2005;
Revised July 5, 2005;
Accepted August 2, 2005
Monitoring Editor: Ben Margolis
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 counterreceptor 
M
2 integrin. We demonstrate that the modulation of JAM-C localization in junctional complexes is a new regulatory mechanism for M2-dependent adhesion of leukocytes.
Abbreviations used: JAM, junctional adhesion molecule; FRAP, fluorescence recovery after photobleaching; EGFP, enhanced green fluorescent protein; HEV, high endothelial venules; FACS, fluorescence-activated cell sorting; ROI, region of interest; DLS, dynamic light scattering; AUC, analytical ultracentrifugation.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Michel Aurrand-Lions (Michel.Aurrand-Lions{at}medecine.unige.ch).
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