Cloning of Human Junctional Adhesion Molecule 3 (JAM3) and Its Identification as the JAM2 Counter-receptor

Abstract

We have identified a third member of the junctional adhesion molecule (JAM) family. At the protein level JAM3 displays 36 and 32% identity to JAM2 and JAM1, respectively. The coding region is distributed over 9 exons and maps to chromosome 11q25. The gene shows widespread tissue expression with higher levels apparent in the kidney, brain, and placenta. At the cellular level we show expression of JAM3 transcript within endothelial cells. Our major finding is that JAM3 and JAM2 are binding partners. Thus, JAM3 ectodomain binds firmly to JAM2-Fc. This heterotypic interaction is maintained when JAM3-Fc is used to capture Chinese hamster ovary cells expressing full-length JAM2. In static adhesion assays we show that JAM3 is unable to bind to leukocyte cell lines. This is consistent with the lack of JAM2 expression. However, using JAM2-Fc pulldown experiments in combination with polyclonal anti-JAM3 serum, we demonstrate that JAM3 is the previously uncharacterized 43-kDa counter-receptor that mediates JAM2 adhesion to T cells. Most significantly we demonstrate up-regulation of JAM3 protein on peripheral blood lymphocytes following activation. Finally we show the utility of JAM3 ectodomain as an inhibitor of JAM2 adhesion.

Junctional adhesion molecule C (JAM-C) distinguishes CD27+ germinal center B lymphocytes from non-germinal center cells and constitutes a new diagnostic tool for B-cell malignancies

“…13 As already described in previous studies, it is also found on hematopoietic cells, such as platelets 14 and activated T cells. 15 In the present study we show that JAM-C is also expressed on human B lymphocytes, in particular on a subset of CD27 þ B cells and that its expression changes during B-cell differentiation. Moreover, JAM-C expression in lymphoproliferative syndromes is disease specific and allows to divide these diseases into JAM-C and JAM-C þ groups.…”

“…21 Arrate et al 15 did not detect JAM-C expression by Northern blot analysis of PBLs, but still detected it on samples from whole-spleen mRNA. To confirm our previous findings, we produced a polyclonal antihuman JAM-C antibody, obtained after immunization of a rabbit with the soluble part of the full-length human JAM-C molecule.…”

“…13 In human tissues, it has also been described on smooth muscle cells and on hematopoietic cells, such as platelets, 14 and activated T cells. 15 JAM-C is also involved in tumor-induced angiogenesis, 16 as well as in leukocyte adhesion and transmigration during inflammation. 17 Our data show that JAM-C expression is regulated during B-cell maturation.…”

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

“…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.…”

The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology

“…However there is no clear consensus regarding the sub-types of Ig-like domains in JAM-A. JAM-B, JAM-C and JAM-L have been reported to contain V-and C2-type domains while JAM4 has been reported to contain a pair of V-type domains (4)(5)(6)(7)(8). With the exception of JAM-L (which lacks a PDZ domain), the JAM family members have been shown to interact with TJ-associated scaffold proteins such as ZO-1, AF6, CASK, MUPP1, PAR3, LNX-1, -2 and MAGI-1 (3,4).…”