Adhesion Molecules of Leukocyte Trafficking :
Junction Adhesion Molecules (JAM's)

JAM

The family of juctional adhesion molecules (JAM), comprising at least three members (i.e., JAM-A, JAM-B and JAM-C), are type I transmembrane receptors belonging to the immunoglobulin (Ig) superfamily. These proteins are localized in the tight junctions between endothelial. Some family members are also found on blood leukocytes and platelets.The basic JAM structure consists two Ig domains, a transmembrane domain and a cytoplasmic domain containing a PDZ-binding motif and a PKC phosphorylation site.

JAM-A

Human JAM-A, also known as platelet adhesion molecule 1 (PAM-1) and platelet F11 receptor, is predominantly expressed at intercellular junctions of both epithelial cellsand endothelial cells. It is also expressed on circulating blood cells including neutrophils, monocytes, platelets, erythrocytes and lymphocytes. JAM-A exhibits homophilic interactions to regulate tight junction assembly and modulate paracellular permeability. This homophilic interation also mediates platelet aggregation and adhesion to endothelial cells and may play a role in thrombosis. JAM-A binds heterotypically with the β 2 integrin lymphocyte function-associated antigen-1 (LFA-1). This JAM-A-LFA-1 interaction is involved in leukocyte adhesion and transmigration. JAM-A has also been shown to bind reovirus attachment protein sigma-1 to permit reovirus infection and signal virus-induced apoptosis.

JAM-B

JAM-B, alternatively named vascular endothelial JAM (VE-JAM), is expressed prominently on high endothelial venules of lymphoid organs where it is localized to the intercellular boundaries of high endothelial cells. It is also expressed on the endothelium of a variety of non-lymphoid organs, especially the heart and placenta. JAM-B exhibits homotypic interactions, as well as heterotypic interactions with JAM-C, but not JAM-A. It is also a ligand for the integrin alpha4beta1. However, the JAM-B/alpha4beta1 interaction is facilitated only after prior adhesion of JAM-B to JAM-C.6 Through its heterotypic interactions with JAM-C, JAM-B is an adhesive ligand for T, NK, and dendritic cells, and may play a role in regulating leukocyte transmigration.

JAM-C

Human JAM-C shows widespread tissue expression and the highest levels are found in the placenta, brain, kidney and heart. JAM-C is expressed on endothelial cells of high endothelial venules in human tonsil. It is also expressed on platelets, T-cells and NK cells. Unlike other JAM family members, JAM-C forms only weak homotypic interactions. JAM-C binds to JAM-B to facilitate the interactions between JAM-B and the integrin alpha4beta1.6 This heterotypic interaction between leukocyte JAM-C and endothelial JAM-B may play a role in regulating leukocyte transmigration. On platelets, JAM-C is a counter-receptor for the leukocyte integrin Mac-1(CD11b/CD18).7 JAM-C has also been identified as a strong candidate gene for hypoplastic left heart syndrome.

PECAM-1

Platelet/endothelial cell adhesion molecule-1 (PECAM-1). also known as CD31, is expressed in large amounts on endothelial cells at intercellular junctions and on T-cell subsets, and to a lesser extent on platelets and most other leukocytes such as monocytes and neutrophils. PECAM-1 binds to itself homotypically, and also to the leukocyte integrin αvβ3 heterotypically. PECAM-1 is required for the transendothelial migration of leukocytes through intercellular junctions of vascular endothelial cells. PECAM-1 has been found in human plasma, and the presence of this circulating isoform is suggested to modulate the transendothelial migration of leukocytes.

VE-Cadherin

Vascular endothelial (VE) - cadherin (VE-CAD), also called 7B4 and cadherin-5, is a member of the cadherin family of cell adhesion molecules. Cadherins are calcium-dependent transmembrane proteins which bind to one another in a homophilic manner. On their cytoplasmic side, they associate with the three catenins, α , β , and γ (plakoglobin). This association links the cadherin protein to the cytoskeleton. Without association with the catenins, the cadherins are non-adhesive. Cadherins play a role in development, specifically in tissue formation. They may also help to maintain tissue architecture in the adult. VE Cadherin has been shown to play important roles in vasculogenesis and angiogenesis. VE-cadherin is a classical cadherin molecule. Classical cadherins consist of a large extracellular domain which contains DXD and DXNDN repeats responsible for mediating calcium-dependent adhesion, a single-pass transmembrane domain, and a short carboxy-terminal cytoplasmic domain responsible for interacting with the catenins.

CD99

CD99 is the third type of endothelial membrane protein that was recently reported to participate in the transmigration. CD99 is a highly O-glycosylated, small protein of only 32 kDa26 with a unique structure without resemblance to any known protein family.