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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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Sprache
englisch
Veröffentlichungsjahr
2004
HGF-Berichtsjahr
0
ISSN (print) / ISBN
0021-9525
e-ISSN
1540-8140
Zeitschrift
Journal of Cell Biology, The
Quellenangaben
Band: 167,
Heft: 6,
Seiten: 1063-1074
Verlag
Rockefeller University Press
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)
PubMed ID
15596545
Erfassungsdatum
2004-12-31