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claudin-3 is not found at the BTB in the rat testis (
Kaitu'u-Lino et al., 2007
).
Thus, much work is needed to define the role(s) of different claudin(s) in
the cyclic restructuring events of the BTB during spermatogenesis.
2.1.2. Occludin
Occludin is the first integral membrane protein identified at the TJ (
Furuse
et al., 1993
). Although occludin shares a similar topography with claudins
by having four transmembrane domains, two extracellular loops and a cyto-
plasmic tail, there is no sequence homology between the two TJ proteins
(
Cummins, 2012
;
Furuse et al., 1998
). Unlike claudins, which are composed
of multiple members in the claudin gene family, no occludin-related gene
has been identified thus far, but two occludin isoforms are produced by
alternative splicing. Also, unlike claudins, occludin has a relative long cyto-
plasmic tail. Ser and Thr residues of its cytoplasmic tail are heavily phos-
phorylated; and studies have shown that phosphorylations at these sites via
protein kinases are essential for regulating occludin localization and distri-
bution in epithelia/endothelia. For instance, a study using primary Sertoli
cell cultures in vitro has demonstrated that focal adhesion kinase (FAK)
is structurally associated with occludin and it also regulates the structural
interaction between occludin and ZO-1 (
Siu et al., 2009a
,
2009b
). Fur-
thermore, a knockdown of FAK in Sertoli cells led to a decrease in phos-
phorylation 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 another nonreceptor
protein tyrosine kinase known to be structurally associated with occludin
at the Sertoli cell BTB (
Xiao et al., 2011
). When the intrinsic activity of
c-Yes in Sertoli cells with an established functional TJ-permeability barrier
that mimicked the BTB in vivo was inhibited by SU6656, a selective c-Yes
inhibitor, redistribution of occludin from cell-cell interface to cell cytosol
was found, contributing to the disruption of the Sertoli cell TJ barrier (
Xiao
et al., 2011
). Besides FAK and c-Yes, protein kinase C (PKC) also plays a
role in modulating the localization of occludin at TJs via its effects to confer
the phosphorylation status in occludin. Study reported that upon stimula-
tion of PKC by phorbol 12-myristate 13-acetate (PMA) and 1,2 dioctan-
oylglycerol (DiC8), phosphorylation of occludin was induced, leading to an
increase in occludin localization at the cell-cell interface (
Andreeva et al.,
2001
). The importance of occludin in spermatogenesis was also addressed
by studies using synthetic occludin peptide. It was demonstrated that when
occludin-occludin interaction between adjacent Sertoli cells was disrupted
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