Argonaute2 regulates the pancreatic β-cell secretome

Sudhir G. Tattikota, Matthias D. Sury, Thomas Rathjen, Hans Hermann Wessels, Amit K. Pandey, Xintian You, Clinton Becker, Wei Chen, Matthias Selbach, Matthew N. Poy

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)1214-1225
Number of pages12
JournalMolecular and Cellular Proteomics
Volume12
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

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