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Open Access Green as soon as Postprint is submitted to ZB.
Nuclear translocation of an ICA512 cytosolic fragment couples granule exocytosis and insulin expression in β-cells.
J. Cell Biol. 167, 1063-1074 (2004)
Islet cell autoantigen 512 (ICA512)/IA-2 is a receptor tyrosine phosphatase-like protein associated with the insulin secretory granules (SGs) of pancreatic beta-cells. Here, we show that exocytosis of SGs and insertion of ICA512 in the plasma membrane promotes the Ca(2+)-dependent cleavage of ICA512 cytoplasmic domain by mu-calpain. This cleavage occurs at the plasma membrane and generates an ICA512 cytosolic fragment that is targeted to the nucleus, where it binds the E3-SUMO ligase protein inhibitor of activated signal transducer and activator of transcription-y (PIASy) and up-regulates insulin expression. Accordingly, this novel pathway directly links regulated exocytosis of SGs and control of gene expression in beta-cells, whose impaired insulin production and secretion causes diabetes.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2004
HGF-reported in Year
0
ISSN (print) / ISBN
0021-9525
e-ISSN
1540-8140
Journal
Journal of Cell Biology, The
Quellenangaben
Volume: 167,
Issue: 6,
Pages: 1063-1074
Publisher
Rockefeller University Press
Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)
PubMed ID
15596545
Erfassungsdatum
2004-12-31