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interaction between afadin and ZO-1 is important for TJ assembly since a
knockdown of either afadin or ZO-1, or over-expression of a truncated form
of afadin that failed to bind to ZO-1 after the knockdown of endogenous
afadin, impeded TJ formation (
Ooshio et al., 2010
). Besides playing a crucial
role in TJ assembly, AJs are also essential for TJ maintenance, as a disruption
of AJs often leads to TJ disassembly. For instance, when E-cadherin-medi-
ated cell-cell adhesion was inhibited by treatment of an anti-E-cadherin
antibody (
Man et al., 2000
), or when E-cadherin was downregulated after
depletion of cellular polyamines (
Guo et al., 2003
), a disruption of the TJ-
permeability barrier was detected, illustrating a primary loss of AJ function
leads to a secondary dysfunction of TJs. More important, cross talk between
AJs and TJs is not unidirectional since AJ integrity is also dependent on
the integrity of TJs. For instance, downregulation of occludin induced by
transfecting PA4 (polyaxonal amacrine 4 cells of retina) epithelial cells with
Raf-1, mislocalization of E-cadherin was observed, suggesting AJ disruption
(
Li and Mrsny, 2000
). Collectively, these findings illustrate that while TJs
and AJs are found in discrete locations in epithelia/endothelia, they are still
functionally connected via their peripheral adaptor proteins. At the BTB,
TJ and basal ES
coexist
in the same location, and such intimate relationship
is especially important to elicit transient “opening” and “closing” of the
barrier during the transit of preleptotene spermatocytes at stage VIII-IX of
the epithelial cycle. It was noted that treatment of adult rats with adjudin
at 50 mg/kg b.w. that was effective to induce germ cell loss from the epi-
thelium except spermatogonia (
Mok et al., 2012b
;
Yan and Cheng, 2005
)
did not impede the BTB integrity. During the process of adjudin-induced
germ cell loss, the adaptor proteins α-catenin and ZO-1 at the basal ES and
TJ, respectively, which were originally tightly associated (“engaged”) for
linking basal ES and TJ together to reinforce the BTB integrity, became
dissociated (“disengaged”). Thus, a primary disruption of the apical ES at
the Sertoli-spermatid interface that facilitates germ cell loss do not perturb
the TJ-barrier function at the BTB since the adaptors that link basal ES
(e.g. catenins) and TJ (e.g. ZO-1) together are “disengaged” during adjudin-
induced germ cell loss (
Yan and Cheng, 2005
). This thus illustrates that a
novel mechanism is in place in the testis to safeguard the BTB integrity in
response to changes in environment, such as following exposure to a toxi-
cant, or during the epithelial cycle of spermatogenesis, when spermatids are
in transit across the seminiferous epithelium involving localized apical ES
restructuring, so that the BTB integrity can be maintained via “disengage-
ment” of basal ES and TJ proteins.
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