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

• Published in: Diabetes, obesity & metabolism Vol. 9; no. s2; pp. 109 - 117
• Main Authors: Izumi, T, Kasai, K, Gomi, H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-11-2007; Blackwell Publishing Ltd
• Subjects: Animals; Binding Sites; Calcium - metabolism; Cell Membrane - physiology; Exocytosis - physiology; granuphilin; Humans; Insulin - metabolism; Insulin-Secreting Cells - physiology; Membrane Fusion - physiology; Mice; Models, Biological; rab GTP-Binding Proteins; rab27 GTP-Binding Proteins; Rab27a; regulated exocytosis; secretory granules; Secretory Vesicles - physiology; tethering; Vesicular Transport Proteins
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2007.00789.x

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 Ca²⁺ concentration from the resting level of ~100 nM to somewhere between ~10 and 100 μM. Although Ca²⁺ 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 Ca²⁺ 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 β cells, and propose a new concept for its functional significance in regulated exocytosis.