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 294

Sertoli cells known as the blood-testis barrier (BTB). The BTB is one of the
tightest blood-tissue barriers, possibly because it is constituted by coexisting
tight junction (TJ), basal ectoplasmic specialization [basal ES, a testis-specific
adherens junction (AJ)], gap junction (GJ), and desmosome (DS) ( Cheng and
Mruk, 2012 ; Wong and Cheng, 2005 ). Except for DS which utilizes vimen-
tin-based intermediate filaments as the attachment site, the above adhesion
junctions are all connected to the actin cytoskeleton, especially the basal ES
which possesses tightly packed actin filament bundles that lie perpendicular
to the Sertoli cell plasma membrane and are sandwiched between cisternae
of endoplasmic reticulum and the opposing Sertoli cell plasma membranes.
This is also the hallmark ultrastructure of the BTB, which contributes to
the unusual adhesive strength of the barrier ( Cheng and Mruk, 2010b , 2011 ;
Mruk et al., 2008 ). Despite the unusual tightness of the BTB, it undergoes
cyclic restructuring during stage VIII-XI of the epithelial cycle to facilitate
the transit of preleptotene spermatocytes at the BTB by assembling “new”
BTB behind the transiting spermatocytes while the “old” BTB above the
spermatocytes is being disassembled, so that the immunological barrier can
remain intact ( Cheng and Mruk, 2011 ; Cheng et al., 2010 ). Thus, the BTB
serves as an immunological barrier to “seal” developing spermatocytes and
spermatids from the systemic circulation, preventing the development of
immune responses against germ cells residing at the apical compartment
which arise at puberty ( Fijak et al., 2011 ; Meinhardt and Hedger, 2011 ).
This hypothesis about the coexistence of an “old” and a “new” BTB that
enclose the spermatocytes in transit at the BTB was designated the inter-
mediate compartment ( Russell, 1977 ), and was shown in a lanthanum study
using electron microscopy from our laboratory ( Yan et al., 2008c ) ( Fig. 6.2 ).
As different types of junctions at the BTB are connected to the actin cyto-
skeleton, BTB restructuring can be effectively regulated via cyclic reor-
ganization of F-actin network utilizing different actin-regulating proteins.
These actin-regulating proteins include epidermal growth factor pathway
substrate 8 (Eps8) ( Lie et al., 2009 ), which is an actin barbed-end cap-
ping and bundling protein ( Hertzog et al., 2010 ), and actin-related protein
3 (Arp3) ( Lie et al., 2010 ), which together with Arp2 forms the Arp2/3
complex that induces branched actin polymerization ( Goley and Welch,
2006 ). Besides, accumulating evidence suggests that mammalian target of
rapamycin (mTOR), a signaling molecule and a nonreceptor protein Ser/
Thr kinase that is known to modulate an array of cellular events ( Weichhart,
2012 ; Zoncu et al., 2011 ), is also responsible for the extensive reorganization
of F-actin network to assist BTB restructuring during the epithelial cycle of
spermatogenesis ( Mok et al., 2012a ; Mok et al., 2012c ).