Exocytosis.

Exocytosis is the fusion of secretory vesicles with the plasma membrane and results in the discharge of vesicle content into the extracellular space and the incorporation of new proteins and lipids into the plasma membrane. Exocytosis can be constitutive (all cells) or regulated (specialized cells such as neurons, endocrine and exocrine cells). Regulated exocytosis is usually, but not always, triggered by an increase in the cytosolic free Ca2+ concentration. In neurons and endocrine cells, a small proportion of regulated secretory vesicles are ready to fuse with the plasma membrane in response to cell stimulation, but the majority are kept in reserve for subsequent stimulation by linkage to a filamentous network of synapsins (in neurons) or actin (in endocrine cells). Regulated exocytosis varies greatly in kinetics and Ca2+ dependency between cell types. It is likely that several different Ca(2+)-binding proteins are involved in regulated exocytosis, with synaptotagmin apparently essential for fast exocytosis at synapses. GTP-binding proteins of both the monomeric and heterotrimeric forms are involved in exocytosis, although their precise role is unclear. Intense current interest focuses on the idea that the molecular mechanism of vesicle docking and fusion is conserved from yeast to mammalian brain. The SNARE hypothesis postulates that vesicle SNAREs (synaptobrevin and homologues) mediate docking by binding to target SNAREs (syntaxin/SNAP-25 and homologues), whereupon SNAPs and NSF bind to elicit membrane fusion.