Vascular Endothelial-Junctional Adhesion Molecule (VE-JAM)/JAM 2 Interacts with T, NK, and Dendritic Cells Through JAM 3

Liang, Tony W.; Chiu, Henry; Gurney, Austin; Sidle, Aiko; Tumas, Daniel B.; Schow, Peter; Foster, Jessica; Klassen, Toni; Dennis, Kathryn; DeMarco, Richard; Pham, Thinh; Frantz, Gretchen; Fong, Sherman

doi:10.4049/jimmunol.168.4.1618

Cited by 126 publications

(127 citation statements)

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“…Decreased occludin expression, such as seen in both the present and previous studies 72 h post-CFA treatment, will disrupt BBB function (Bolton et al, 1998;Brooks et al, 2005;Brown and Davis, 2005;Hawkins and Davis, 2005;Huber et al, 2002a). Similarly, modulation of JAM-1 protein expression and/or localization is linked to a decrease in normal barrier function, and increased paracellular transport (Dobrogowska and Vorbrodt, 2004;Liang et al, 2002;Mandell and Parkos, 2005). In the present study, we show alterations in the protein expression and localization of occludin, JAM-1 and claudin-5 which correlate to an early (24 h) and a late (72 h) period of increased BBB paracellular permeability to [ 14 C]sucrose.…”

Section: Discussionsupporting

confidence: 56%

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

et al. 2006

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The blood-brain barrier (BBB) is a dynamic system which maintains brain homeostasis and limits CNS penetration via interactions of transmembrane and intracellular proteins. Inflammatory pain (IP) is a condition underlying several diseases with known BBB perturbations, including stroke, Parkinson's, multiple sclerosis and Alzheimer's. Exploring the underlying pathology of chronic IP, we demonstrated alterations in BBB paracellular permeability with correlating changes in tight junction (TJ) proteins: occludin and claudin-5. The present study examines the IP-induced molecular changes leading to a loss in functional BBB integrity. IP was induced by injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the right hindpaw of female Sprague-Dawley rats. Inflammation and hyperalgesia were confirmed, and BBB paracellular permeability was assessed by in situ brain perfusion of [ 14 C]sucrose (paracellular diffusion marker). The permeability of the BBB was significantly increased at 24 and 72 h post-CFA. Analysis of the TJ proteins, which control the paracellular pathway, demonstrated decreased claudin-5 expression at 24 h, and an increase at 48 and 72 h post-injection. Occludin expression was significantly decreased 72 h post-CFA. Expression of junction adhesion molecule-1 (JAM-1) increased 48 h and decreased by 72 h post-CFA. Confocal microscopy demonstrated continuous expression of both occludin and JAM-1, each co-localizing with ZO-1. The increased claudin-5 expression was not limited to the junction. These results provide evidence that chronic IP causes dramatic alterations in specific cytoarchitectural proteins and demonstrate alterations in molecular properties during CFA, resulting in significant changes in BBB paracellular permeability.

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Section: Discussionsupporting

confidence: 56%

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

et al. 2006

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“…Interestingly, multiple members of the JAM protein family have also been shown to act as receptors for viruses (Bergelson et al 1997, Barton et al 2001 and have been shown to localize to intercellular junctions (Martin-Padura et al 1998, Liu et al 2000, Cohen et al 2001. The JAM proteins are type I transmembrane proteins consisting of an N-terminal signal peptide, an extracellular domain, a single membrane-spanning domain and a short cytoplasmic tail (Malergue et al 1998, MartinPadura et al 1998, Ozaki et al 1999, Williams et al 1999, Cunningham et al 2000, Liu et al 2000, Palmeri et al 2000, Sobocka et al 2000, Arrate et al 2001, Aurrand-Lions et al 2001a,b, Naik et al 2001, Liang et al 2002, Santoso et al 2002, Hirabayashi et al 2003, Moog-Lutz et al 2003. The extracellular domains of JAMs consist of two immunoglobulin-like loops, each containing an intradomain disulfide bond while the cytoplasmic tails of several members terminate in putative PDZ-binding motifs that appear to mediate binding to intercellular junction-associated scaffold proteins (Cunningham et al 2000, Ebnet et al 2000, 2001, Martinez-Estrada et al 2001, Hamazaki et al 2002, Santoso et al 2002, Hirabayashi et al 2003.…”

Section: The Molecular Basis Of Pmn Transepithelial Migrationmentioning

confidence: 99%

Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation

Reaves

Chin

Parkos

2005

Mem. Inst. Oswaldo Cruz

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“…The cytoplasmic tail of JAM1 contains a PDZ-binding motif putatively involved in the binding of JAM1 to the cytoplasmic TJ-associated protein ZO-1 (8,9). Three homologs to JAM1 have been reported as follows: JAM-2, which is expressed primarily on endothelial cells (10,11); JAM-3, which is expressed on leukocytes (12)(13)(14); and JAM-4, which was recently reported in kidney and intestinal epithelia (15).…”

mentioning

confidence: 99%

Involvement of the Junctional Adhesion Molecule-1 (JAM1) Homodimer Interface in Regulation of Epithelial Barrier Function

Mandell

McCall

Parkos

2004

Journal of Biological Chemistry

113

120

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Junctional adhesion molecule-1 (JAM1) is a tight junction-associated immunoglobulin superfamily protein implicated in the regulation of tight junctions and leukocyte transmigration. The structural basis for the function of JAM1 has yet to be determined. Here we provide evidence that JAM1 homodimer formation is important for its function in epithelial cells. Experiments were conducted to determine the effects of a panel of JAM1 monoclonal antibodies on epithelial barrier recovery after transient disruption by calcium switch. Two monoclonal antibodies were observed to inhibit barrier recovery in contrast to another monoclonal antibody that had no effect. Epitope mapping by phage display revealed that both inhibitory antibodies bind to a region of JAM1 located within the N-terminal Ig-like loop (residues 111-123). Competition experiments with synthetic peptides and site-directed mutagenesis confirmed the location of this epitope. Analysis of the crystal structure of JAM1 revealed that this epitope includes residues within the putative homodimer interface, and one of the two inhibitory antibodies was then shown to block JAM1 homodimer formation in vitro. Finally, mutations within the homodimer interface were shown to prevent enrichment of JAM1 at points of cell contact, presumably by interference with homophilic interactions. These findings suggest that homodimer formation may be important for localization of JAM1 at tight junctions and for regulation of epithelial barrier function.A crucial function of epithelial cells is in the maintenance of a selective barrier separating the external from internal environments. It is well known that tight junctions (TJs) 1 play an important role in the maintenance and regulation of these barriers. Located at the apical-most part of the lateral epithelial cell membrane, TJs regulate paracellular diffusion of ions and small molecules across epithelial barriers. In addition, TJs serve as a fence between the apical and basolateral domains of polarized cells and facilitate bi-directional signal transduction between the intracellular and extracellular environments. TJs are composed of both transmembrane and cytoplasmic structural elements. Transmembrane protein members include occludins, claudins, coxsackie adenovirus receptors, and junctional adhesion molecules (JAMs). Knowledge of how these various proteins contribute to TJ function is continually evolving.JAM1 is an immunoglobulin superfamily protein that localizes to TJs of epithelial and endothelial cells (1) as well as to the surface of leukocytes (2). Evidence suggests a role for JAM1 in TJ assembly (3). Exogenous expression of JAM1 in CHO cells has been shown to promote localization of ZO-1 and occludin at points of cell contact (4). Monoclonal antibodies to JAM1 have been shown to inhibit reassembly of TJs and block recovery of transepithelial resistance to ion flux (3). Similar effects on epithelial barrier function were observed with recombinant soluble JAM1 consisting of the extracellular domain fused to IgG Fc (5). In add...

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Vascular Endothelial-Junctional Adhesion Molecule (VE-JAM)/JAM 2 Interacts with T, NK, and Dendritic Cells Through JAM 3

Cited by 126 publications

References 15 publications

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation

Involvement of the Junctional Adhesion Molecule-1 (JAM1) Homodimer Interface in Regulation of Epithelial Barrier Function

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