Regulation of Blood–Testis Barrier (BTB) Dynamics during Spermatogenesis via the “Yin” and “Yang” Effects of Mammalian Target of Rapamycin Complex 1 (mTORC1) and mTORC2 - International Review of Cell and Molecular Biology - page 339

which are connected in “clones,” at the BTB. Figure 6.5 depicts a hypo-
thetical model regarding the involvement of mTORC1 and mTORC2 in
regulating BTB integrity during the epithelial cycle of spermatogenesis. It is
hypothesized that during the epithelial cycle, upregulation of rictor at stages
I-VII that favors the formation of mTORC2 is being used to maintain the
BTB integrity, but not at stages VIII-IX when its expression is downregu-
lated at the time of BTB restructuring. On the other hand, during stage late
VIII-IX, the transient-induced expression of raptor favors the formation
of mTORC1 for the disruption of the “old” BTB at the apical region of
the transiting preleptotene spermatocytes at the site. This process is further
facilitated by the reduction in mTORC2 due to a downregulation of ric-
tor ( Figs 6.4 and 6.5 ). Furthermore, the low level of rictor expressed during
the BTB restructuring may be necessary for the “assembly” and “mainte-
nance” of the “new” BTB that is being created at the basal region of the
transiting preleptotene spermatocytes ( Fig. 6.5 ). In fact, the dependence of
relative abundance of raptor and rictor for the activation of mTORC1 or
mTORC2 signaling has been demonstrated in other studies. For example,
it was reported that the knockdown of raptor by RNAi in HEK-293T and
HeLa cells led to an increase in PKB phosphorylation on S473, indicat-
ing mTORC2 signaling was enhanced. On the other hand, in the same
cell types, knockdown of rictor caused increased phosphorylation of S6K1
with increased association between raptor and mTOR, revealing mTORC1
signaling was stimulated ( Sarbassov et al., 2004 ). More important, it was
revealed that in mTOR-mediated mitochondrial metabolism, a knock-
down of raptor reduced oxygen consumption while a knockdown of rictor
increased oxygen consumption and oxidative capacity ( Schieke et al., 2006 ).
These studies thus illustrate how a cellular function can be modulated based
on the “yin-and-yang” effects of the two mTOC complexes mediated by
the relative availability of raptor and rictor in a cellular microenvironment.
In short, the combined antagonistic effects of the mTORC1 or mTORC2
signaling complexes can fine-tune a cellular event, such as the migration of
preleptotene spermatocytes across the BTB as depicted in Fig. 6.5 .
5. CONCLUDING REMARKS AND FUTURE
PERSPECTIVES
In this chapter, we have provided a critical update on the biology of
adhesion junctions as well as the role of constituent proteins in regulating
BTB dynamics in the testis. We have also reviewed the functional relationship