RGD Reference Report - rpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9. - Rat Genome Database

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rpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9.

Authors: Mok, KW  Mruk, DD  Cheng, CY 
Citation: Mok KW, etal., J Cell Sci. 2014 Nov 15;127(Pt 22):4870-82. doi: 10.1242/jcs.152231. Epub 2014 Sep 12.
RGD ID: 11041641
Pubmed: (View Article at PubMed) PMID:25217631
DOI: Full-text: DOI:10.1242/jcs.152231

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 BTB. These findings were confirmed by the use of a specific MMP-9 inhibitor that blocked the disruption of the tight junction permeability barrier by the rpS6 mutant. Additionally, RNA interference (RNAi)-mediated Akt silencing was able to mimic the results of rpS6 mutant overexpression in Sertoli cells, further confirming this p-rpS6-Akt-MMP-9 signaling pathway. In conclusion, these data support a new concept of mTORC1-mediated BTB regulation, that is possibly also applicable to other blood-tissue barriers.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Rps6  (ribosomal protein S6)


Additional Information