Argonaute2 regulates the pancreatic β-cell secretome.
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.
Max Delbrueck Center for Molecular Medicine, Robert Rössle Strasse 10, 13125 Berlin, Germany.
Sudhir G
SG
Tattikota
Matthias D
MD
Sury
Thomas
T
Rathjen
Hans-Hermann
HH
Wessels
Amit K
AK
Pandey
Xintian
X
You
Clinton
C
Becker
Wei
W
Chen
Matthias
M
Selbach
Matthew N
MN
Poy
D000818:Animals; D060565:Argonaute Proteins / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D007328:Insulin; D035683:MicroRNAs; C540349:Mirn375 microRNA, mouse; D020543:Proteome