Argonaute2 Regulates the Pancreatic β-Cell Secretome

• Published in: Molecular & cellular proteomics 2013-05, Vol.12 (5), p.1214-1225
• Main Authors: Tattikota, Sudhir G., Sury, Matthias D., Rathjen, Thomas, Wessels, Hans-Hermann, Pandey, Amit K., You, Xintian, Becker, Clinton, Chen, Wei, Selbach, Matthias, Poy, Matthew N.
• Format: Article
• Language: English
• Subjects: Animals; Argonaute Proteins - physiology; Cell Line; Gene Expression Regulation; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - metabolism; Mice; Mice, Inbred C57BL; MicroRNAs - metabolism; Proteome - genetics; Proteome - metabolism; RNA Interference
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.M112.024786

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 β-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 β-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 β-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 β-cell by influencing the secretory pathway. This study specifically addresses the role of Ago2 in the systemic release of proteins from β-cells and highlights the contribution of the microRNA pathway to the function of this cell type.