JAM

Junctional adhesion molecules (JAMs) belong to the immunoglobulin superfamily and were the first tight junction proteins to be identified in both endothelial and epithelial cells (Martin-Padura I et al. 1998). JAMs have three unique structural domains, including an extracellular segment with two variable-type immunoglobulin-like domains and a single transmembrane segment with a C-terminal intracellular domain (Martin-Padura I et al. 1998).

All three JAMs contain tyrosine and serine/threonine at their cytoplasmic termini. Despite the early discovery of JAMs, the effects of their involvement in signal transduction on the regulation of TJ functions have not been well studied compared to other TJ proteins.

The JAM family is composed of two groups (Bazzoni G 2003). The first group comprises JAM-A/F11r/CD321, JAM-B/CD322 and JAM-C/CD323 and has a class II PDZ domain-binding motif at the C-terminus that binds to ZO-1 and PAR-3.

The other group has a class I PDZ domain binding motif at the C-terminus (Ebnet K et al. 2001; Ebnet K et al. 2003) and includes the coxsackie and adenovirus receptor (CAR), the endothelial cell-selective adhesion molecule (ESAM) and JAM-D. JAMs are often associated with the recruitment of other TJ molecules such as occludin and intracellular binding partners with PDZ domain proteins such as ZO-1, AF-6, CASK, PAR-3 and MUPP-1 (Ebnet K et al. 2001). Together, these partners may play an important role in TJ assembly, actin cytoskeleton reorganization and regulation of cell polarity.

JAMs also play an important role in the barrier function of TJs and in the development of apico-basal cell polarity in epithelial cells (Martin-Padura I et al. 1998). For example, one study shows that antibodies against JAM-A increase monolayer permeability in a human retinal pigment epithelial cell line. Furthermore, inhibition of JAM-A reduces fibroblast growth factor(FGF)-induced proliferation and migration of endothelial cells (Naik MU et al. (2003).

Some evidence suggests that JAM expression by endothelial cells may be important for proper angiogenesis. In addition, the skin vessels of mice show significantly reduced leukocyte infiltration in contact dermatitis-induced skin inflammation when treated with neutralizing antibodies against JAM-B and JAM-C. Furthermore, it can be assumed that JAMs are involved in the inflammation and regulate leukocyte infiltration (Ludwig RJ et al. 2005).

1. Bazzoni G (2003) The JAM family of junctional adhesion molecules. Curr Opin Cell Biol 15: 525-530).
2. Ebnet K et al. (2001) The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J 20: 3738-3748.
3. Ebnet K et al. (2003) The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: A possible role for JAMs in endothelial cell polarity. J. Cell Sci 116: 3879-3891)
4. Ludwig RJ et al. (2005) Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation. J Investig Dermatol 125: 969-976.
5. Martin-Padura I et al. (1998) Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol 142, 117-127.
6. Naik MU et al. (2003) Essential role of junctional adhesion molecule-1 in basic fibroblast growth factor-induced endothelial cell migration. Arterioscler Thromb Vasc Biol 23: 2165-2171.