Identified at the BTB inside the rat testis (Kaitu’u-Lino et al., 2007). Thus, much operate is required to define the function(s) of distinctive claudin(s) within the cyclic restructuring events on the BTB for the duration of spermatogenesis. two.1.2. Occludin–Occludin would be the initial integral membrane protein identified at the TJ (Furuse et al., 1993). Despite the fact that occludin shares a similar topography with CYP1 manufacturer claudins by having 4 transmembrane domains, two extracellular loops along with a cytoplasmic tail, there’s no sequence homology in between the two TJ proteins (Cummins, 2012; Furuse et al., 1998). In contrast to claudins, that are composed of several members within the claudin gene family members, no occludin-related gene has been identified as a result far, but two occludin isoforms are developed by alternative splicing. Also, in contrast to claudins, occludin has a relative extended cytoplasmic tail. Ser and Thr residues of its cytoplasmic tail are heavily phosphorylated; and research have shown that phosphorylations at these sites by way of protein kinases are necessary for regulating occludin localization and distribution in epithelia/endothelia. For instance, a study applying primary Sertoli cell cultures in vitro has demonstrated that focal adhesion kinase (FAK) is structurally connected with occludin and additionally, it regulates the structural interaction involving occludin and ZO-1 (Siu et al., 2009a, 2009b). Furthermore, a knockdown of FAK in Sertoli cells led to a GLUT4 web reduce in phosphorylation of Ser and Tyr, but not Thr in occludin, which, in turn, probably resulted in an increase in the internalization of occludin, thereby perturbing the TJ barrier (Siu et al., 2009a). Besides FAK, c-Yes is a different nonreceptor protein tyrosine kinase identified to become structurally linked 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; obtainable 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 identified, contributing for the disruption from the Sertoli cell TJ barrier (Xiao et al., 2011). In addition to FAK and c-Yes, protein kinase C (PKC) also plays a function 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,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 significance of occludin in spermatogenesis was also addressed by studies using synthetic occludin peptide. It was demonstrated that when occludin ccludin interaction amongst adjacent Sertoli cells was disrupted by means of intratesticular injection of peptide corresponding to a segment from 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 6 weeks at the time the initial wave of spermatogenesis occurred (Saitou et al., 2000). Having said that, these occludin knockout mice had been discovered 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 producing a further genetic model of occludin knockdo.
