Identified in the BTB in the rat testis (Kaitu’u-Lino et al., 2007). Therefore, substantially operate is needed to define the part(s) of different claudin(s) inside the cyclic restructuring events from the BTB in the course of spermatogenesis. two.1.two. Occludin–Occludin may be the initial integral membrane protein identified in the TJ (Furuse et al., 1993). Despite the fact that occludin shares a similar topography with claudins by obtaining 4 transmembrane domains, two extracellular loops and a cytoplasmic tail, there is no sequence homology in between the two TJ proteins (Cummins, 2012; Furuse et al., 1998). In contrast to claudins, that are composed of multiple members in the claudin gene family, no occludin-related gene has been identified hence far, but two occludin isoforms are created by option splicing. Also, unlike claudins, occludin includes a relative extended cytoplasmic tail. Ser and Thr residues of its cytoplasmic tail are heavily phosphorylated; and studies have shown that phosphorylations at these web sites via protein HIV-1 medchemexpress kinases are critical for regulating occludin localization and distribution in epithelia/endothelia. As an illustration, a study working with principal Sertoli cell cultures in vitro has demonstrated that focal adhesion kinase (FAK) is structurally linked with occludin and additionally, it regulates the structural interaction among occludin and ZO-1 (Siu et al., 2009a, 2009b). In addition, 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, possibly resulted in an increase inside the internalization of occludin, thereby perturbing the TJ barrier (Siu et al., 2009a). Apart from FAK, c-Yes is a different nonreceptor protein IL-2 drug tyrosine kinase recognized to be structurally connected with occluding at 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; out there 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 of the Sertoli cell TJ barrier (Xiao et al., 2011). Apart from FAK and c-Yes, protein kinase C (PKC) also plays a part in modulating the localization of occludin at TJs by means of 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 in the cell ell interface (Andreeva et al., 2001). The importance of occludin in spermatogenesis was also addressed by research utilizing synthetic occludin peptide. It was demonstrated that when occludin ccludin interaction among adjacent Sertoli cells was disrupted by means of intratesticular injection of peptide corresponding to a segment in the second extracellular loop of occludin, the BTB was compromised, major to germ cell loss from the epithelium (Chung et al., 2001). Interestingly, when occludin was deleted, occludin knockout mice remained fertile by age six weeks at the time the initial wave of spermatogenesis occurred (Saitou et al., 2000). On the other hand, these occludin knockout mice have 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 an additional genetic model of occludin knockdo.
