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Argonaute2 regulates the pancreatic β-cell secretome

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Item Type:Article
Title:Argonaute2 regulates the pancreatic β-cell secretome
Creators Name:Tattikota, S.G. and Sury, M.D. and Rathjen, T. and Wessels, H.H. and Pandey, A.K. and You, X. and Becker, C. and Chen, W. and Selbach, M. and Poy, M.N.
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 beta-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 beta-cell secretome and we identified using quantitative mass spectrometry the enhanced release of a set of proteins or secretion signature in response to a glucose stimulus using the murine beta-cell line, MIN6. In addition, 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 beta-cell by influencing the secretory pathway. This study specifically addresses the role of Ago2 in the systemic release of proteins from beta-cells and highlights the contribution of the microRNA pathway to the function of this cell type.
Keywords:Argonaute Proteins, Cell Line, Gene Expression Regulation, Insulin, Insulin-Secreting Cells, MicroRNAs, Proteome, RNA Interference, Animals, Mice
Source:Molecular & Cellular Proteomics
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:1214-1225
Date:May 2013
Official Publication:https://doi.org/10.1074/mcp.M112.024786
PubMed:View item in PubMed

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