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

This Article Full Text (PDF, 936K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuma, R. Search for Related Content PubMed Articles by Tuma, R. Social Bookmarking                            What's this?

Measuring insulin

ICA512 (red) cleavage by µ-calpain (green) sends a signal to make more insulin.

Pancreatic ß cells that exocytose insulin must make more insulin. Trajkovski et al., on page 1063, now demonstrate that the signal to induce insulin synthesis after exocytosis comes from the cleavage of the cytoplasmic domain of islet cell autoantigen 512 (ICA512). This protein fragment migrates to the nucleus and drives changes in gene expression.Previous work showed that ICA512 is a transmembrane protein associated with insulin-containing secretory granules of ß cells and that exocytosis of the organelles leads to the insertion of ICA512 into the plasma membrane. Now, using a combination of antibodies and GFP-labeled ICA512 proteins, the team find that once ICA512 is inserted into the plasma membrane, its cytoplasmic tail is cleaved by Ca²⁺-activated µ-calpain. The liberated cytoplasmic domain moves to the nucleus where it binds PIASy, which is known to regulate various transcription factors.

Transient transfection of the cytoplasmic domain of ICA512 was sufficient to induce expression of insulin mRNA. Furthermore, when Trajkovski et al. blocked calpain activity with either calpeptin or RNAi, insulin expression was not induced, indicating that cleavage of ICA512 was required to induce gene transcription.

Putting these data together, the team proposes that Ca²⁺ acts a dual trigger, coupling the release of insulin with a feedback signal that modulates gene expression in proportion to the secretory activity of the cell. Because ICA512 is found on secretory granules in virtually all neuroendocrine cells, the researchers think the feedback system may be involved in a wide variety of hormone and neuropeptide biosynthesis and secretion systems.

Rabiya Tuma

rabiya{at}nasw.org

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF, 936K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuma, R. Search for Related Content PubMed Articles by Tuma, R. Social Bookmarking                            What's this?