Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members

Endothelial cells are linked to each other through intercellular junctional complexes that regulate the barrier and fence function of the vascular wal l. The nature of these intercellular contacts varies with the need for perm eability: For example, in brain the impervious blood-brain barrier is maint ained by "tight" contacts between endothelial cells. By contrast, in high e ndothelial venules (HEVs), where lymphocytes continuously exit the bloodstr eam, the contacts are generally leaky. The precise molecular components tha t define the type of junction remain to be characterized. An immunoglobulin superfamily molecule named JAM-2, specifically expressed in lymphatic endo thelial cells and HEVs, was recently identified. JAM-3 was cloned and chara cterized in the current study, and JAM-1, -2, and -3 were shown to form a n ovel protein family belonging to the larger cortical thymocyte Xenopus (CTX ) molecular family. Using antibodies specific for each of the 3 family memb ers, their specific participation in different types of cell-cell contact i n vivo and their specific and differential localization in lateral contacts or tight junctions were demonstrated. Furthermore, it was shown that JAM-1 and JAM-2 differentially regulate paracellular permeability, suggesting th at the presence of JAM-1, -2, or -3 in vascular junctions may play a role i n regulating vascular function in vivo. (C) 2001 by The American Society of Hematology.