Nuclear translocation of an ICA512 cytosolic fragment couples granule exocytosis and insulin expression in {beta}-cells.
J Cell Biol
; 167(6): 1063-74, 2004 Dec 20.
Article
em En
| MEDLINE
| ID: mdl-15596545
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Núcleo Celular
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Ilhotas Pancreáticas
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Proteínas Tirosina Fosfatases
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Grânulos Citoplasmáticos
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Exocitose
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Insulina
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Proteínas de Membrana
Limite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Alemanha