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Nuclear translocation of an ICA512 cytosolic fragment couples granule exocytosis and insulin expression in β-cells

Published inThe journal of cell biology, vol. 167, no. 6, p. 1063-1074
Publication date2004-12-20
First online date2004-12-13
Abstract

Islet cell autoantigen 512 (ICA512)/IA-2 is a receptor tyrosine phosphatase-like protein associated with the insulin secretory granules (SGs) of pancreatic β-cells. Here, we show that exocytosis of SGs and insertion of ICA512 in the plasma membrane promotes the Ca2+-dependent cleavage of ICA512 cytoplasmic domain by μ-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 β-cells, whose impaired insulin production and secretion causes diabetes.

Affiliation Not a UNIGE publication
Citation (ISO format)
TRAJKOVSKI, Mirko et al. Nuclear translocation of an ICA512 cytosolic fragment couples granule exocytosis and insulin expression in β-cells. In: The journal of cell biology, 2004, vol. 167, n° 6, p. 1063–1074. doi: 10.1083/jcb.200408172
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ISSN of the journal0021-9525
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