Upported by studies illustrating that overexpression of exogenous occludin in fibroblasts was able to induce the formation of TJ strands, but these TJ strands had been shorter and lesser in quantity when in comparison to those claudin-based TJ strands; and when fibroblasts had been cotransfected with occludin and claudins, occludin was recruited for the TJ strands formed by claudins, and with each other they formed continuous belt-like ultrastructures at the cell ell interface, which was in contrast to the punctuate pattern when occludin was overexpressed alone (Furuse et al., 1998). Extra crucial, though young adult occludin knockout mice at 610 weeks of age were fertile but when these mice reached adulthood by 30 weeks, in addition to being infertile with seminiferous tubules had been found to be devoid of spermatocytes and spermatids, calcification within the brain, and chronic gastritis within the gastric epithelium had been detected (Saitou et al., 2000), illustrating occludin, and maybe TJs, may possibly be playing far more vital cellular roles in addition to serving as an indispensable protein in the TJ barrier. Within this context, it is actually of interest to note that studies have reported internalization of occludin by caveolae and/or clathrin-mediated endocytosis (Murakami et al., 2009; Schwarz et al., 2007; Shen and Turner, 2005), including the Sertoli cell TJ barrier (Wong et al., 2009; Yan et al., 2008c), illustrating occludin could be swiftly mobilized to other cellular domains to exert its function apart from the TJ barrier. 2.1.3. Junctional Adhesion Molecules–JAMs are members from the immunoglobulin superfamily (IgSF) proteins; the extracellular area of these TJ-integral membrane proteins possess two Ig-like domains. According to sequence homology, JAM household is composed of two subfamilies with one of them comprises three closely connected members namely JAM-A (JAM-1), JAM-B (JAM-2) and JAM-C (JAM-3). Yet another subfamily, in which the members possess a reduced polypeptide sequence similarity, involves Auto, JAM-D (JAM-4) and JAMlike (JAM-L). Herein, we focus on the former subfamily given that its members have been much better characterized and studied in the testis. JAMs differ from claudins and occludin topologically considering that each and every JAM molecule has only a single extracellular domain, a single transmembrane area and a cytoplasmic tail that varies in length among various isoforms (Mandell and Parkos, 2005; Severson and Parkos, 2009). As opposed to claudins and occludin, JAMs alone is insufficient to from TJ strands as no TJs had been detected in a lot of key cultures of fibroblasts and established fibroblast cell lines that expressed either JAM-A or JAM-C. Even so, JAMs are concentrated towards the TJs when examined by immunofluorescence microscopy (PTH Proteins MedChemExpress Morris et al., 2006). JAMs are also distributed in and about TJ strands under electron microscopy, indicating their intimate association using the TJ barrier (Itoh et al., 2001). The involvementNIH-PA Author MCP-1/CCL2 Protein Protocol manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptInt Rev Cell Mol Biol. Author manuscript; readily available in PMC 2014 July 08.Mok et al.Pageof JAM proteins in TJ-barrier function has been revealed in numerous studies. As an example, a study in T84 human intestinal epithelial cells using anti-JAM-A antibody has shown that JAM-A is necessary for recovery of Ca2+ depletion-induced TJ-barrier disruption as reestablishment of TJ barrier was disrupted resulting from the loss of JAM-A and occludin function following antibody treatment (Liu et al., 2000). JAMs are also essential for the resealing of.
