Located at the BTB in the rat testis (Kaitu’u-Lino et al., 2007). Hence, significantly function is necessary to define the function(s) of distinct claudin(s) inside the cyclic restructuring events with the BTB throughout spermatogenesis. two.1.2. Occludin–Occludin is the 1st integral membrane protein identified in the TJ (Furuse et al., 1993). Although occludin shares a equivalent topography with claudins by obtaining 4 transmembrane domains, two extracellular loops and a BChE drug cytoplasmic tail, there’s no sequence homology involving the two TJ proteins (Cummins, 2012; Furuse et al., 1998). In contrast to claudins, that are composed of several members inside the claudin gene family members, no occludin-related gene has been identified as a result far, but two occludin isoforms are made by option splicing. Also, as opposed to claudins, occludin includes a relative long cytoplasmic tail. Ser and Thr residues of its cytoplasmic tail are heavily phosphorylated; and studies have shown that phosphorylations at these web-sites by means of protein kinases are critical for regulating occludin localization and distribution in epithelia/endothelia. For instance, a study employing major Sertoli cell cultures in vitro has demonstrated that focal adhesion kinase (FAK) is structurally linked with occludin and it also regulates the structural interaction amongst occludin and ZO-1 (Siu et al., 2009a, 2009b). Additionally, a knockdown of FAK in Sertoli cells led to a decrease in phosphorylation of Ser and Tyr, but not Thr in occludin, which, in turn, most likely Aurora A list resulted in an increase inside the internalization of occludin, thereby perturbing the TJ barrier (Siu et al., 2009a). In addition to FAK, c-Yes is one more nonreceptor protein tyrosine kinase recognized to become structurally related 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; offered 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 located, contributing towards the disruption in 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 through its effects to confer the phosphorylation status in occludin. Study reported that upon stimulation of PKC by phorbol 12-myristate 13-acetate (PMA) and 1,2 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 research making use of synthetic occludin peptide. It was demonstrated that when occludin ccludin interaction involving adjacent Sertoli cells was disrupted through intratesticular injection of peptide corresponding to a segment on the second extracellular loop of occludin, the BTB was compromised, major to germ cell loss in the epithelium (Chung et al., 2001). Interestingly, when occludin was deleted, occludin knockout mice remained fertile by age six weeks in the time the very first wave of spermatogenesis occurred (Saitou et al., 2000). Nonetheless, these occludin knockout mice have been found to be infertile by 400 weeks of age, with their seminiferous tubules displayed atrophy and devoid of germ cells (Saitou et al., 2000). Subsequent research by generating a further genetic model of occludin knockdo.