Measuring insulin

Pancreatic β 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 β 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...