Biology Reference
In-Depth Information
Stage VII
Stage late VIII
Elongated spermatid
Sertoli cell
MMP2
Laminin
fragment
Laminin 333
Cleavage
Extensive
F-actin
network
α
6
β
1 integrin
Degradation
BTB
Preleptotene
spermatocyte
Transcytosis
Preleptotene
spermatocyte
Nu
Nu
Nu
Nu
Hemidesmosome
Basement
membrane
Keys:
Basal ES protein
(
e.g.
N-cadherin)
TJ-protein
(
e.g.
occludin)
GJ-protein
(
e.g.
connexin-43)
Translocation of spermatocyte
ZO-1
Disrupted hemidesmosome
(
e.g.
-c
atenin
1-integrin)
-c
atenin
Figure 6.2
Restructuring of the BTB to facilitate the transit of preleptotene spermatocytes
at stage VIII of the epithelial cycle.
Before BTB restructuring takes place, its integrity is main-
tained by
coexisting
TJs, basal ES and GJs which interact with each other and linked to actin
cytoskeleton for structural support via adaptor proteins such as ZO-1. Besides, desmosome
is also present at the Sertoli cell-cell interface at the BTB. On the other hand, elongated
spermatids are also anchored to the Sertoli cell via a testis-specific apical ES protein com-
plex in which laminin-333 residing at the elongating spermatid is linked to
α
6
β
1-integrin
restricted to the Sertoli cell. At stage VIII of the epithelial cycle, when preleptotene sper-
matocytes are in transit at the BTB to enter the apical compartment for further develop-
ment, the “old” BTB above the spermatocyte disassembles to “open” the BTB. This process
is mediated by the apical ES-BTB-hemidesmosome functional axis, in which laminin 333
at the apical ES is cleaved by MMP2 to generate bioactive laminin fragments. The laminin
fragments induce disruption of the “old” BTB and cause the loss of hemidesmosome func-
tion which also contributes to the “opening” of the “old” BTB. Besides, BTB restructuring is
also facilitated by mTORC1 as well as by the reorganization of actin cytoskeleton mediated
by actin-regulating proteins, such as the Arp2/3-N-WASP complex and Eps8 which induce
a “branched/debundled” and “bundled” configuration of the actin filaments at the basal ES,
respectively. Without the support from the dense F-actin network, BTB proteins are inter-
nalized through endocytosis and the internalized BTB proteins can either undergo degra-
dation or being recycled for the assembly of “new” BTB via transcytosis at the base of the
preleptotene spermatocytes. It is likely that molecules, such as testosterone, that promote
BTB integrity may be working in concert with mTORC2 underneath the spermatocyte in
transit to
assemble
a “new” BTB before the “old” BTB above the transiting spermatocyte is
dis-
assembled
, so that the barrier function can remain intact during germ cell movement at the
site. For color version of this igure, the reader is referred to the online version of this topic.
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