Argonaute2 regulates the pancreatic ?-cell secretome.

ABSTRACT: Argonaute2 (Ago2) is an established component of the microRNA-induced silencing complex. Similar to miR-375 loss-of-function studies, inhibition of Ago2 in the pancreatic ?-cell resulted in enhanced insulin release underlining the relationship between these two genes. Moreover, as the most abundant microRNA in pancreatic endocrine cells, miR-375 was also observed to be enriched in Ago2-associated complexes. Both Ago2 and miR-375 regulate the pancreatic ?-cell secretome, and by using quantitative mass spectrometry, we identified the enhanced release of a set of proteins or secretion "signatures " in response to a glucose stimulus using the murine ?-cell line MIN6. In addition, the loss of Ago2 resulted in the increased expression of miR-375 target genes, including gephyrin and ywhaz. These targets positively contribute to exocytosis indicating they may mediate the functional role of both miR-375 and Ago proteins in the pancreatic ?-cell by influencing the secretory pathway. This study specifically addresses the role of Ago2 in the systemic release of proteins from ?-cells and highlights the contribution of the microRNA pathway to the function of this cell type.

SUBMITTER: Tattikota SG 

PROVIDER: S-EPMC3650333 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature