RpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9.

ABSTRACT: Mammalian target of rapamycin complex 1 (mTORC1) is an emerging regulator of blood-tissue barriers that utilizes ribosomal protein S6 (rpS6) as the downstream signaling molecule. To explore the role of rpS6 in blood-testis barrier (BTB) function, a constitutively active quadruple rpS6 phosphomimetic mutant was constructed in mammalian expression vector and overexpressed in Sertoli cells cultured in vitro that mimicked the BTB in vivo. Using this quadruple phosphomimetic mutant, phosphorylated (p)-rpS6 was shown to disrupt IGF-1/insulin signaling, thereby abolishing Akt phosphorylation, which led to an induction of MMP-9. This increase in MMP-9 secretion perturbed the Sertoli cell tight junction permeability barrier by proteolysis-mediated downregulation of tight junction proteins at the BT

SUBMITTER: Mok KW 

PROVIDER: S-EPMC4231304 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature