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Journal of Cell Science, Vol 113, Issue 13 2363-2374, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
Y Liu, A Nusrat, FJ Schnell, TA Reaves, S Walsh, M Pochet and CA Parkos
Division of Gastrointestinal Pathology, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Epithelial cells form a highly selective barrier and line many organs. The epithelial barrier is maintained by closely apposed cell-cell contacts containing tight junctions, the regulation of which is incompletely understood. Here we report the cloning, tissue localization and evidence for a role in epithelial barrier regulation of an immunoglobulin superfamily member that likely represents the human homolog of murine junction adhesion molecule (JAM). Analysis of the primary structure of human JAM, cloned from T84 epithelial cells, predicts a transmembrane protein with an extracellular domain that contains two IgV loops. Monoclonal antibodies generated against the putative extracellular domain were reactive with a 35-39 kDa protein from both T84 epithelial cells and human neutrophils. By immunofluorescence, JAM mAbs labeled epithelial cells from intestine, lung, and kidney, prominently in the region of tight junctions (co-localization with occludin) and also along lateral cell membranes below the tight junctions. Flow cytometric studies confirmed predominant JAM expression in epithelial cells but also revealed expression on endothelial and hematopoietic cells of all lineages. Functional studies demonstrated that JAM specific mAbs markedly inhibited transepithelial resistance recovery of T84 monolayers after disruption of intercellular junctions (including tight junctions) by transient calcium depletion. Morphologic analysis revealed that, after disassembly of cell-cell junctions, anti-JAM inhibition of barrier function recovery correlated with a loss of both occludin and JAM, but not ZO-1, in reassembling tight junction structure. Reassembly of the major adherens junction component E-cadherin was not affected by JAM specific mAbs. Our findings suggest that JAM plays an important role in the regulation of tight junction assembly in epithelia. Furthermore, these JAM-mediated effects may occur by either direct, or indirect interactions with occludin.
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Y. Liu, H.-J. Buhring, K. Zen, S. L. Burst, F. J. Schnell, I. R. Williams, and C. A. Parkos Signal Regulatory Protein (SIRPalpha ), a Cellular Ligand for CD47, Regulates Neutrophil Transmigration J. Biol. Chem., March 15, 2002; 277(12): 10028 - 10036. [Abstract] [Full Text] [PDF] |
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T. W. Liang, H. H. Chiu, A. Gurney, A. Sidle, D. B. Tumas, P. Schow, J. Foster, T. Klassen, K. Dennis, R. A. DeMarco, et al. Vascular Endothelial-Junctional Adhesion Molecule (VE-JAM)/JAM 2 Interacts with T, NK, and Dendritic Cells Through JAM 3 J. Immunol., February 15, 2002; 168(4): 1618 - 1626. [Abstract] [Full Text] [PDF] |
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M. Aurrand-Lions, C. Johnson-Leger, C. Wong, L. Du Pasquier, and B. A. Imhof Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members Blood, December 15, 2001; 98(13): 3699 - 3707. [Abstract] [Full Text] [PDF] |
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T. Kucharzik, S. V. Walsh, J. Chen, C. A. Parkos, and A. Nusrat Neutrophil Transmigration in Inflammatory Bowel Disease Is Associated with Differential Expression of Epithelial Intercellular Junction Proteins Am. J. Pathol., December 1, 2001; 159(6): 2001 - 2009. [Abstract] [Full Text] [PDF] |
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S. K. Shaw, B. N. Perkins, Y.-C. Lim, Y. Liu, A. Nusrat, F. J. Schnell, C. A. Parkos, and F. W. Luscinskas Reduced Expression of Junctional Adhesion Molecule and Platelet/Endothelial Cell Adhesion Molecule-1 (CD31) at Human Vascular Endothelial Junctions by Cytokines Tumor Necrosis Factor-{alpha} Plus Interferon-{gamma} Does Not Reduce Leukocyte Transmigration Under Flow Am. J. Pathol., December 1, 2001; 159(6): 2281 - 2291. [Abstract] [Full Text] [PDF] |
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M. P. Arrate, J. M. Rodriguez, T. M. Tran, T. A. Brock, and S. A. Cunningham Cloning of Human Junctional Adhesion Molecule 3 (JAM3) and Its Identification as the JAM2 Counter-receptor J. Biol. Chem., November 30, 2001; 276(49): 45826 - 45832. [Abstract] [Full Text] [PDF] |
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Y. Liu, D. Merlin, S. L. Burst, M. Pochet, J. L. Madara, and C. A. Parkos The Role of CD47 in Neutrophil Transmigration. INCREASED RATE OF MIGRATION CORRELATES WITH INCREASED CELL SURFACE EXPRESSION OF CD47 J. Biol. Chem., October 19, 2001; 276(43): 40156 - 40166. [Abstract] [Full Text] [PDF] |
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M. Itoh, H. Sasaki, M. Furuse, H. Ozaki, T. Kita, and S. Tsukita Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions J. Cell Biol., August 6, 2001; 154(3): 491 - 498. [Abstract] [Full Text] [PDF] |
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T. A. Reaves, S. P. Colgan, P. Selvaraj, M. M. Pochet, S. Walsh, A. Nusrat, T. W. Liang, J. L. Madara, and C. A. Parkos Neutrophil transepithelial migration: regulation at the apical epithelial surface by Fc-mediated events Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G746 - G754. [Abstract] [Full Text] [PDF] |
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U. Naik, M. Naik, K Eckfeld, P Martin-DeLeon, and J Spychala Characterization and chromosomal localization of JAM-1, a platelet receptor for a stimulatory monoclonal antibody J. Cell Sci., January 2, 2001; 114(3): 539 - 547. [Abstract] [PDF] |
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A. Nusrat, J. R. Turner, and J. L. Madara Molecular Physiology and Pathophysiology of Tight Junctions: IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells Am J Physiol Gastrointest Liver Physiol, November 1, 2000; 279(5): G851 - G857. [Abstract] [Full Text] [PDF] |
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V. B. Serikov, Y. J. Jang, and J. H. Widdicombe Estimate of the subepithelial hydrostatic pressure that drives inflammatory transudate into the airway lumen J Appl Physiol, April 1, 2002; 92(4): 1702 - 1708. [Abstract] [Full Text] [PDF] |
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S. A. Cunningham, M. P. Arrate, J. M. Rodriguez, R. J. Bjercke, P. Vanderslice, A. P. Morris, and T. A. Brock A Novel Protein with Homology to the Junctional Adhesion Molecule. CHARACTERIZATION OF LEUKOCYTE INTERACTIONS J. Biol. Chem., October 27, 2000; 275(44): 34750 - 34756. [Abstract] [Full Text] [PDF] |
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O. M. Martinez-Estrada, A. Villa, F. Breviario, F. Orsenigo, E. Dejana, and G. Bazzoni Association of Junctional Adhesion Molecule with Calcium/calmodulin-dependent Serine Protein Kinase (CASK/LIN-2) in Human Epithelial Caco-2 Cells J. Biol. Chem., March 16, 2001; 276(12): 9291 - 9296. [Abstract] [Full Text] [PDF] |
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