Chromogranin B regulates early stage insulin granule trafficking from the Golgi in pancreatic islet β-cells

Abstract

Chromogranin B (CgB) is abundantly expressed in dense core secretory granules of multiple endocrine tissues and has been suggested to regulate granule biogenesis in some cell types, including the pancreatic islet β-cell, though the mechanisms are poorly understood. Here we demonstrate a critical role for CgB in regulating secretory granule trafficking in the β-cell. Loss of CgB impairs glucose-stimulated insulin secretion, impedes proinsulin processing yielding increased proinsulin content, and alters the density of insulin-containing granules. Using an in situ fluorescent pulse-chase strategy to track nascent proinsulin, we show that loss of CgB impairs Golgi budding of proinsulin-containing secretory granules resulting in a substantial delay in trafficking nascent granules to the plasma membrane with an overall decrease in total plasma membrane-associated granules. These studies demonstrate that CgB is necessary for efficient trafficking of secretory proteins into the budding granule, which impacts the availability of insulin-containing secretory granules for exocytic release.