Identified at the BTB in the rat testis (Kaitu’u-Lino et al., 2007). Therefore, a lot work is needed to define the part(s) of distinctive claudin(s) in the cyclic restructuring events on the BTB through spermatogenesis. two.1.2. Occludin–Occludin will be the initial integral membrane protein identified at the TJ (Furuse et al., 1993). Despite the fact that occludin shares a related topography with claudins by obtaining four transmembrane domains, two extracellular loops and a cytoplasmic tail, there is no sequence homology among the two TJ proteins (Cummins, 2012; Furuse et al., 1998). Unlike claudins, which are composed of several members within the claudin gene family, no occludin-related gene has been identified therefore far, but two occludin isoforms are developed by option splicing. Also, unlike claudins, occludin features a relative extended cytoplasmic tail. Ser and Thr residues of its cytoplasmic tail are heavily phosphorylated; and studies have shown that phosphorylations at these internet sites by way of protein kinases are necessary for regulating occludin localization and distribution in epithelia/endothelia. For instance, a study employing primary Sertoli cell cultures in vitro has demonstrated that focal adhesion kinase (FAK) is structurally related with occludin and it also regulates the structural interaction among occludin and ZO-1 (Siu et al., 2009a, 2009b). Furthermore, a knockdown of FAK in Sertoli cells led to a reduce in phosphorylation of Ser and Tyr, but not Thr in occludin, which, in turn, most likely resulted in a rise within the internalization of occludin, thereby perturbing the TJ barrier (Siu et al., 2009a). In addition to FAK, c-Yes is a different nonreceptor protein tyrosine kinase known to be structurally connected with occluding in the Sertoli cell BTB (Xiao et al., 2011). When the intrinsic activity of c-Yes in Sertoli cells with an establishedInt Rev Cell Mol Biol. Author manuscript; readily available in PMC 2014 July 08.Mok et al.Pagefunctional TJ-permeability barrier that mimicked the BTB in vivo was inhibited by SU6656, a selective c-Yes inhibitor, redistribution of occludin from cell ell interface to cell cytosol was found, contributing to the disruption with the Sertoli cell TJ barrier (Xiao et al., 2011). Apart from FAK and c-Yes, protein kinase C (PKC) also plays a function in modulating the localization of occludin at TJs by way of its effects to confer the phosphorylation status in occludin. Study reported that upon GNE-371 References stimulation of PKC by phorbol 12-myristate 13-acetate (PMA) and 1,two dioctanoylglycerol (DiC8), phosphorylation of occludin was induced, major to a rise in occludin localization at the cell ell interface (Andreeva et al., 2001). The importance of occludin in spermatogenesis was also addressed by studies utilizing synthetic occludin peptide. It was demonstrated that when occludin ccludin interaction in Angiopoietin-Like 8 Proteins Storage & Stability between adjacent Sertoli cells was disrupted via intratesticular injection of peptide corresponding to a segment from the second extracellular loop of occludin, the BTB was compromised, top to germ cell loss in the epithelium (Chung et al., 2001). Interestingly, when occludin was deleted, occludin knockout mice remained fertile by age 6 weeks at the time the very first wave of spermatogenesis occurred (Saitou et al., 2000). Nevertheless, these occludin knockout mice had been found to become infertile by 400 weeks of age, with their seminiferous tubules displayed atrophy and devoid of germ cells (Saitou et al., 2000). Subsequent studies by creating a different genetic model of occludin knockdo.