Here come the newcomer granules, better late than never

Exocytosis in pancreatic β-cells employs Munc18/soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes that mediate the priming and docking onto the plasma membrane (PM) of insulin granules, called predocked granules, that sit on the PM until Ca(2+) influx evokes fusion. This accounts for most of the initial peak secretory response. However, the subsequent sustained phase of glucose-stimulated insulin secretion arises from newcomer granules that have a minimal residence time at the PM before fusion. In this Opinion I discuss recent work that has begun to decipher the components of the exocytotic machinery of newcomer granules, including a Munc18/SNARE complex that is different from that mediating the fusion of predocked granules and which can potentially rescue defective insulin secretion in diabetes. These insights are applicable to other neuroendocrine cells that exhibit sustained secretion.