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Junctional adhesion molecule (JAM) family
Published in C. Yan Cheng, Spermatogenesis, 2018
Proteins of the JAM family are type I glycoprotein belonging to the immunoglobulin superfamily (IgSF). The JAM family consists of seven members including three classical members (JAM-A, JAM-B, and JAM-C) and four nonclassical members (CAR, endothelial cell-selective adhesion molecule [ESAM], JAM-L, and JAM-4).1–10 Like other junction protein families, the nomenclature of JAM proteins is diverse because JAMs have been identified by several research groups. For instance, VE-JAM and human JAM-2 are the aliases of JAM-B. Efforts were made in 2003 to standardize the nomenclature of the classical JAMs and designate them as JAM-A, JAM-B, and JAM-C.11 All JAM family proteins are characterized by a V-type and a C2-type immunoglobulin-like domain in their extracellular domain followed by a transmembrane segment and a cytoplasmic tail with a PDZ-binding motif (Phe-Leu-Val) (Figure 5.1). The three classical JAMs share up to 32% of amino acid sequence identity12 and also share ~15% sequence homology with the nonclassical JAM members. The nonclassical JAMs are diverged from the classical JAM by their cytoplasmic tails.13 The cytoplasmic tails of the classical JAMs are relatively conserved in length and motif composition.14 PDZ-containing proteins such as ZO-1, AF-6, CASK, PAR-3, and MUPP-1 bind onto the PDZ motif of JAM-A15–18 while ZO-1 and PAR-3 bind to JAM-B and JAM-C.19 ZO-1, MUPP-1, and LNX2 bind to CAR.20–22 Interaction of PDZ motif with various PDZ-containing proteins is involved in intracellular signal transduction and an array of cellular functions including cell polarity, cell migration, and barrier permeability (Table 5.1). In the extracellular domain, a tripeptide motif (Arg-Val-Glu for JAM-A, Arg-Leu-Glu for JAM-B, and Arg-Ile-Glu for JAM-C) in the V-type domain acts as a dimerization motif and another tripeptide linker sequence (Val-Leu-Val) connects the two immunoglobulin domains to impose a bent conformation (Figure 5.1).23–25
F11R/JAM-A: why do platelets express a molecule which is also present in tight junctions?
Published in Platelets, 2023
Piotr Kamola, Anna Babinska, Tomasz Przygodzki
In 1990, Kornecki et al. showed that certain antibodies which had the capability of activating human blood platelets were binding to a protein target which was not known at the time. The protein was named F11 receptor (F11R) after the name of the clone of these antibodies (F11).1 Platelet activation induced by binding of the antibodies to F11R was primarily shown to be dependent on the interaction of Fc fragment of F11 antibodies with FcγRII receptor present on blood platelets5 (Figure 1). In 1998, a similar protein was isolated during studies on tight junctions in epithelial and endothelial cell monolayers.2 The protein was recognized as an immunoglobulin and named after its function as Junctional Adhesion Molecule (JAM). In the wake of full sequencing of the protein, the homology of JAM-A and F11R was established.6,7 As an effect of this convergent discovery, the two names of the protein exist simultaneously in scientific publications. This status quo gained legitimacy by the decision of the Human Genome Nomenclature committee which has approved F11R as a symbol of the gene number AF207907, and the number BC021876 for the murine molecule, while JAM-A was mentioned as one of the alias symbols among others such as PAM-1, JCAM, JAM-1, JAMA, and CD321.
Epithelial integrity, junctional complexes, and biomarkers associated with intestinal functions
Published in Tissue Barriers, 2022
Arash Alizadeh, Peyman Akbari, Johan Garssen, Johanna Fink-Gremmels, Saskia Braber
JAM-A is generally believed to have dual functions. Within the immune system, it has been implicated to control the recruitment of leukocytes to the site of inflammation, whereas along intestinal epithelial cells, dominant expression of JAM-A has been observed in the region of TJs, suggesting a critical role in barrier function.64,72,78,79 Homophilic interaction of JAM-A between adjacent cells is mediated through membrane-distal extracellular Ig-like domains (Figure 2) forming a barrier against luminal substances. The short cytoplasmic domain of JAM-A terminates with PDZ-binding motifs that interact with different cytoplasmic scaffolding proteins, including ZO-1, ZO-2 and cingulin (Figures 2 and 4) by which it is linked to the intracellular cytoskeleton.64,72,80 Although JAM-A knockout mice display a normal epithelial architecture, intestinal integrity tests confirm an increased gut permeability to different paracellular markers and a decreased TEER in mucosal tissue samples obtained from these animals.78,81 In addition, it has been shown that JAM-A is involved in the recovery of epithelial barrier function after disruption of TJs by transient calcium depletion, since inhibition of JAM-A leads to retarded TJs reassembly in human T84 epithelial cells shown by disrupted redistribution of OCLN and decreased TEER recovery.79
Targets for MAbs: innovative approaches for their discovery & validation, LabEx MAbImprove 6th antibody industrial symposium, June 25-26, 2018, Montpellier, France
Published in mAbs, 2019
Pierre Martineau, Hervé Watier, Andre Pèlegrin, Andrei Turtoi
JAM-A. To identify new potential targets, functional approaches were developed using tumor cells as immunogens, to select mAbs targeting membrane receptors involved in cell proliferation. Cancer cells were injected into mice and the resulting hybridomas were screened for their ability to inhibit cell proliferation in vitro. Based on this functional approach coupled to proteomic analysis, a mAb specifically recognizing the human junctional adhesion molecule-A (JAM-A) was identified. JAM-A is mainly overexpressed on breast, lung, and kidney tumor tissues. In vivo experiments demonstrated that injections of anti-JAM-A mAb resulted in a significant tumor growth inhibition of xenografted human tumors. Treatment with Hz6F4 induced a decrease in Ki67 expression and downregulated JAM-A levels. The results also demonstrate that a functional approach coupled to a robust proteomic analysis can be successful to identify new antibody target molecules in oncology.11