Disease relevance of JAM3

• The expression of JAM-related proteins by endothelial cells prompted us to test whether recruitment of the ternary complex in endothelial cells can occur through binding to JAM-2, JAM-3, endothelial cell-selective adhesion molecule (ESAM) or coxsackie- and adenovirus receptor (CAR) [1].
• Together, through modulation of endothelial contractility and VE-cadherin-mediated adhesion, JAM-C helps to regulate vascular permeability and pathologic angiogenesis [2].
• The homophilic interaction of JAM-C can mediate tumor cell-endothelial cell interactions and may thereby be involved in the process of tumor cell metastasis [3].
• The role of junctional adhesion molecule C (JAM-C) in acute pancreatitis [4].

High impact information on JAM3

• Strikingly, disruption of JAM-C function decreased basal permeability and prevented the VEGF- and histamine-induced increases in human dermal microvascular endothelial cell permeability in vitro and skin permeability in mice [2].
• Here, the role of JAM-C in vascular permeability was investigated in vitro and in vivo [2].
• JAM-C was essential for the regulation of endothelial actomyosin, as revealed by decreased F-actin, reduced myosin light chain phosphorylation, and actin stress fiber formation due to JAM-C knockdown [2].
• Furthermore, JAM-C and CAR, two tight junction integral membrane proteins, are also components of apical ES involving in spermatid orientation [5].
• JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration [6].

Biological context of JAM3

• Most significantly we demonstrate up-regulation of JAM3 protein on peripheral blood lymphocytes following activation [7].
• Within this critical region we have identified JAM3, a member of the junction adhesion molecule family, as a strong candidate gene for the cardiac phenotype on the basis that it is expressed during human cardiogenesis in the structures principally affected in hypoplastic left heart [8].
• Here, the homophilic interaction of JAM-C is presented and functionally characterized to mediate tumor cell-endothelial cell interactions [3].
• Mutagenesis of the only acidic residue in the C-D loop of this Ig fold, namely Asp-82, has no bearing on alpha(4)beta(1) interactions, and thus JAM2 deviates somewhat from the mechanism used by other immunoglobulin superfamily cell adhesion molecules to engage integrin [9].
• We show that transfection of JAM-C improves the tight junctional barrier in tumor cells devoid of JAM-C expression [6].

Anatomical context of JAM3

• At the cellular level we show expression of JAM3 transcript within endothelial cells [7].
• We have previously reported that junctional adhesion molecule 2 (JAM2) adheres to T cells through heterotypic interactions with JAM3 [9].
• In static adhesion assays we show that JAM3 is unable to bind to leukocyte cell lines [7].
• Vascular endothelial-junctional adhesion molecule (VE-JAM)/JAM 2 interacts with T, NK, and dendritic cells through JAM 3 [10].
• Desmosomal localization of JAM-C was further confirmed by experiments aimed at selective disruption of tight junctions and desmosomes [11].

Associations of JAM3 with chemical compounds

• The junctional adhesion molecule C (JAM-C) was recently shown to undergo a heterophilic interaction with the leukocyte beta2 integrin Mac-1, thereby mediating interactions between vascular cells in inflammatory cell recruitment [3].
• This is dependent on serine 281 in the cytoplasmic tail of JAM-C because serine mutation into alanine abolishes the specific localization of JAM-C in tight junctions and establishment of cell polarity [6].

Regulatory relationships of JAM3

• Previous studies have shown that key adhesive interactions between leukocyte CD11b/CD18 and basally expressed fucosylated glycoproteins followed by binding to desmosomal-associated JAM-C are key elements of the transmigration response [12].

Other interactions of JAM3

• JAM-C is a component of desmosomes and a ligand for CD11b/CD18-mediated neutrophil transepithelial migration [11].
• The deletion includes FLI-1, but not JAM-3, which will help to determine the critical genes involved in this syndrome [13].

References