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 340

between these proteins and the underlying actin cytoskeleton. While some
of the discussions are based on findings in other epithelia/endothelia, this
information will be helpful to design functional experiments in future stud-
ies to unravel the regulation of the BTB. We also provide an update on the
latest development regarding the involvement of the two mTOR signaling
complexes, namely mTORC1 and mTORC2, in regulating BTB dynamics
during the seminiferous epithelial cycle of spermatogenesis. Although
recent studies have shown that the mTORC1 and mTORC2 signaling
complexes likely modulate BTB dynamics their antagonistic effects on the
TJ-permeability barrier function via actin cytoskeleton, however, the actin
regulatory proteins involved in these events remain to be identified and exam-
ined. Much work is needed to explore if mTOR complexes exert their effects
on the F-actin via drebrin E, paladin, formins, filamins, Eps8, the Arp2/3
complex and others. Other small GTPases such as Rac and Rho and polarity
proteins (e.g. PAR3, PAR6, 14-3-3, Scribble/Dlg/Lgl) may also be involved.
Moreover, the molecular mechanism(s) by which rictor regulates the expression
of GJ proteins and GJ communication, which in turn modulates BTB dynam-
ics, remains to be identified. Additionally, we hypothesize that mTORC1
and mTORC2 regulate BTB dynamics via their antagonistic effects on BTB
assembly and maintenance, and the activity of these two signal complexes are
mediated by the relative expression of their key binding partners raptor and
rictor and downstream signaling molecules, such as rpS6, in the seminiferous
epithelium. While much work is needed, however, the model depicted in Fig.
6.5 provides a framework upon which functional studies can be designed to
understand the interplay between mTOR complexes and other regulatory
proteins that modulate the BTB function during spermatogenesis.
ACKNOWLEDGMENTS
Studies conducted in the authors' laboratory were supported by grants from the National
Institutes of Health (NICHD, U54 HD029990 Project 5 to CYC, R01 HD056034 to CYC).
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