期刊
MOLECULAR & CELLULAR PROTEOMICS
卷 12, 期 5, 页码 1214-1225出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/mcp.M112.024786
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资金
- European Research Council [260744] Funding Source: Medline
- European Research Council (ERC) [260744] Funding Source: European Research Council (ERC)
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 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 beta-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 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.
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