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 290

4. RegulationofBTBDynamicsbymTOR 335

4.1. Background 335

4.2. RegulationofBTBDynamicsbymTORC1 338

4.3. RegulationofBTBDynamicsbymTORC2 339

4.4. AHypotheticModelBasedonTheAntagonisticEfectsofmTORC1
andmTORC2onBTBFunctiontoRegulate
itsIntegrityduringTheEpithelialCycleofSpermatogenesis

340

5. ConcludingRemarksandFuturePerspectives 341

Abstract
Inmammalian testes, haploid spermatozoa are formed from diploid spermatogonia
duringspermatogenesis,which isacomplicatedcellularprocess.Whilethesecellular
eventswerereportedinthe1960sand1970s,theunderlyingmolecularmechanism(s)
that regulates these events remained unexplored until the past ∼ 10 years. For
instance, adhesionproteinswere shown tobe integrated components at the Sertoli
cell-cell interface and/or the Sertoli-spermatid interface in the late 1980s. But only
until recently, studies have demonstrated that some of the adhesion proteins serve
as the platform for signal transduction that regulates cell adhesion. In this chapter,
abrief summaryandcriticaldiscussionareprovidedon the latest findings regarding
these cell-adhesion proteins in the testis and their relationship to spermatogenesis.
Moreover, antagonistic effects of twomammalian target of rapamycin (mTOR) com-
plexes,knownasmTORC1andmTORC2,oncell-adhesionfunctioninthetestisaredis-
cussed.Finally,ahypotheticmodelispresentedtodepicthowthesetwomTOR-signal-
ingcomplexeshavingthe“yin”and“yang”antagonisticeffectsontheSertolicelltight
junction(TJ)-permeabilitybarriercanmaintaintheblood-testisbarrier(BTB) integrity
duringtheepithelialcyclewhilepreleptotenespermatocytesarecrossingtheBTB.

ABBREVIATIONS

AJ adherens junction, also known as zonula adherens
AMPK AMP-activated protein kinase
Arp2/3 complex actin-related protein 2/3 complex
BTB blood-testis barrier
Caco-2 cells human colonic epithelial-2 cells
CAR coxsackievirus and adenovirus receptor
Cx connexin
Deptor DEP domain-containing mTOR-interacting protein, an inhibitor of mTORC1
and mTORC2
Dlg discs large
DS desmosome
4E-BP1 4E-binding protein 1
EC ectodomain module
Eps8 epidermal growth factor pathway substrate 8
ERK1/2 extracellular regulated kinase ½
ES ectoplasmic specialization