TY - JOUR
T1 - Argonaute2 regulates the pancreatic β-cell secretome
AU - Tattikota, Sudhir G.
AU - Sury, Matthias D.
AU - Rathjen, Thomas
AU - Wessels, Hans Hermann
AU - Pandey, Amit K.
AU - You, Xintian
AU - Becker, Clinton
AU - Chen, Wei
AU - Selbach, Matthias
AU - Poy, Matthew N.
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
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U2 - 10.1074/mcp.M112.024786
DO - 10.1074/mcp.M112.024786
M3 - Article
C2 - 23358505
AN - SCOPUS:84877614776
SN - 1535-9476
VL - 12
SP - 1214
EP - 1225
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 5
ER -