Secretory vesicle docking to the plasma membrane: molecular mechanism and functional significance

In regulated exocytic pathways, secretion occurs only in the presence of appropriate stimuli. Professional secretory cells harbour specific storage organelles that release bioactive substances with both controlled timing and quantity in response to the strength and period of stimulation. Although each secretory organelle is highly differentiated in multicellular organisms, the basic regulatory mechanism is thought to be conserved. In most instances, the secretagogue increases the intracellular Ca(2+) concentration from the resting level of approximately 100 nM to somewhere between approximately 10 and 100 microM. Although Ca(2+) sensors of the final fusion reaction, such as synaptotagmin, have been investigated intensively in synaptic vesicle exocytosis, there are other preceding rate-limiting steps influenced by Ca(2+) and other secretory signals, especially in the exocytosis of secretory granules whose time course is much slower than that of synaptic vesicles. The stable docking of secretory vesicles to the fusion site that is only seen in regulated exocytic pathways may represent one such critical step. Here, we review the molecular mechanism of docking, mainly based on recent findings on insulin granules in pancreatic beta cells, and propose a new concept for its functional significance in regulated exocytosis.