NDLI: Regulation of insulin granule turnover in pancreatic beta-cells by cleaved ICA512.

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Regulation of insulin granule turnover in pancreatic beta-cells by cleaved ICA512.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kalaidzidis, Yannis Solimena, Michele Schubert, Sandra Mziaut, Hassan Altkrüger, Anke Trajkovski, Mirko
Description	Author Affiliation: Trajkovski M ( Laboratory of Experimental Diabetology, School of Medicine, Dresden University of Technology, Dresden 01307, Germany.)
Abstract	Insulin maintains homeostasis of glucose by promoting its uptake into cells from the blood. Hyperglycemia triggers secretion of insulin from pancreatic beta-cells. This process is mediated by secretory granule exocytosis. However, how beta-cells keep granule stores relatively constant is still unknown. ICA512 is an intrinsic granule membrane protein, whose cytosolic domain binds beta2-syntrophin, an F-actin-associated protein, and is cleaved upon granule exocytosis. The resulting cleaved cytosolic fragment, ICA512-CCF, reaches the nucleus and up-regulates the transcription of granule genes, including insulin and ICA512. Here, we show that ICA512-CCF also dimerizes with intact ICA512 on granules, thereby displacing it from beta2-syntrophin. This leads to increased granule mobility and insulin release. Based on these findings, we propose a model whereby the generation of ICA512-CCF first amplifies insulin secretion. The ensuing reduction of granule stores would then increase the probability of newly generated ICA512-CCF to reach the nucleus and enhance granule biogenesis, thus allowing beta-cells to constantly adjust production of granules to their storage size and consumption. Pharmacological modulation of these feedback loops may alleviate deficient insulin release in diabetes.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	48
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-11-28
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Nucleus Enzymology Insulin-Secreting Cells Insulin Secretion Membrane Proteins Metabolism Receptor-Like Protein Tyrosine Phosphatases, Class 8 Secretory Vesicles Active Transport, Cell Nucleus Genetics Animals Cell Line Diabetes Mellitus, Type 1 Dystrophin-Associated Proteins Exocytosis Homeostasis Mice Mice, Knockout Protein Structure, Tertiary Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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