Biology Reference
In-Depth Information
Stage I-VI
Stage late VIII-IX
Sertoli cell
mTORC2 is
predominantly
assembled
mTORC1 is
predominantly
assembled
mTORC1 is
predominantly
assembled
mTORC2 is
predominantly
assembled
Maintenance
Maintenance
Preleptotene
spermatocyte
Formati
on of
“new” BTB
Preleptotene
spermatocyte
Nu
Nu
Nu
Nu
Hemidesmosome
Basement
membrane
Keys:
Translocation of
spermatocyte
F-actin
mTOR
Raptor
Basal ES protein
(
e.g.
N-cadherin)
TJ-protein
(
e.g.
occludin)
GJ-protein
(
e.g.
connexin-43)
Rictor
mTORC1
mTORC2
GTPase
A yet-to-be
defined
mechanism
ZO-1
-c
atenin
-c
atenin
PKC-
Figure 6.5
mTORC1 and mTORC2 display antagonistic effects on the BTB and their
combined effects can protect the immunological barrier integrity during the transit of
preleptotene spermatocytes at the BTB.
It is noted that rictor and raptor compete for
mTOR for the formation of mTORC2 and mTORC1, respectively, to promote BTB and dis-
rupt BTB integrity. At stages I-VI in which prior to BTB restructuring, the relative high
expression of rictor favors the assembly of mTORC2, which is necessary for keeping the
integrity of BTB by maintaining the dense F-actin network (namely the actin filament
bundles at the basal ES), expression level of GJ proteins and GJ communication. On the
other hand, in stage late VIII to stage IX that the BTB is transiently “open” to facilitate the
transit of spermatocyte, the expression level of raptor is induced, whereas that of rictor
is reduced. Thus, formation of mTORC2 is reduced and mTORC1 is favored. mTORC1 acti-
vates rpS6, which in turn disrupts the “old” BTB above the preleptotene spermatocytes in
transit at the BTB by inhibiting de novo synthesis of BTB proteins. In addition, actin cyto-
skeleton reorganization during BTB restructuring is induced by (i) mTORC1 signaling via
S6K1 and rpS6 and (ii) the decrease in phosphorylated PKC-
α
due to reduced mTORC2.
The disorganized F-actin network leads to internalization of BTB proteins, which per-
turbs the “old” BTB. Furthermore, the decrease in GJ proteins and GJ communication
caused by reduced mTORC2 also facilitates the disruption of the “old” BTB for the translo-
cation of spermatocytes across the BTB. However, while mTORC2 expression is reduced,
it remains to be robust enough to sustain the maintenance of the “new” BTB that is
being assembled behind the preleptotene spermatocytes in transit. In short, utilizing
the antagonistic effects of the mTORC1 and mTORC2 on the TJ-permeability barrier, the
immunological barrier function can be maintained during the passage of preleptotene
spermatocytes, which are connected in “clones” via intercellular bridges, at the BTB. For
color version of this igure, the reader is referred to the online version of this topic.
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