The ability to regulate the secretion of proteins is crucial to physiology, behavior and development. Eukaryotic cells express a constitutive secretory pathway that enables the immediate secretion of newly synthesized proteins. Neurons and endocrine cells, among others, also express a regulated secretory pathway, which enables them to store a subset of secretory proteins (e.g., neuropeptides, peptide hormones) into a class of vesicles that accumulate intracellularly and whose exocytosis can be triggered by the appropriate extracellular physiological stimulus. The vesicles that mediate this regulated secretion are called large dense core vesicles (LDCVs). LDCVs form at the trans-Golgi network where their soluble cargo aggregates to form a dense core, but the cellular mechanisms, and in particular, the cytosolic machinery that produces these secretory vesicles have remained elusive for many years.
