JCB logo
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 13 December 2004. doi:10.1083/jcb.200408172
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 6, 1063-1074
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 5966K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Trajkovski, M.
Right arrow Articles by Solimena, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Trajkovski, M.
Right arrow Articles by Solimena, M.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

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



Mirko Trajkovski1, Hassan Mziaut1, Anke Altkrüger1, Joke Ouwendijk1, Klaus-Peter Knoch1, Stefan Müller2, and Michele Solimena1

1 Experimental Diabetology, Carl Gustav Carus Medical School, Dresden University of Technology, Dresden 01307, Germany
2 Department of Molecular Cell Biology, Max Planck Institute for Biochemistry, Martinsried 82152, Germany

Correspondence to Michele Solimena: michele.solimena{at}mailbox.tu-dresden.de

Islet cell autoantigen 512 (ICA512)/IA-2 is a receptor tyrosine phosphatase-like protein associated with the insulin secretory granules (SGs) of pancreatic ß-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 ß-cells, whose impaired insulin production and secretion causes diabetes.

Abbreviations used in this paper: APP, amyloid precursor protein; CPE, carboxypeptidase E; FRET, fluorescence resonance energy transfer; ICA512, Islet Cell Autoantigen 512; ICA512-CCF, ICA512-cleaved cytosolic fragment; ICA512-TMF, ICA512-transmembrane fragment; INS-1, insulinoma cells-1; PIAS, protein inhibitor of activated STAT; PTP, protein tyrosine phosphatase; SG, secretory granule; siRNA, short-interfering RNA; STAT, signal transducer and activator of transcription.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Measuring insulin
Rabiya Tuma
J. Cell Biol. 2004 167: 992. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents