Calcium-Dependent Exocytosis, Biophysical Models of

Abstract

Synonyms Non-constitutive exocytosis; Regulated exocytosis Definition Calcium-dependent exocytosis is the biochemically controlled fusion of the bilipid secretory vesicle membrane with the bilipid cell membrane, triggered by the binding of several Ca 2+ ions to control proteins such as synaptotagmins anchored at the interface between these two membranes. Exocy-tosis results in the release of vesicle contents into the extracellular space, namely, the release of neurotransmitter into the synaptic cleft in the case of neuronal synapses and neuromuscular junctions or the secretion of hormone into the bloodstream in the case of endocrine cells. Exocytosis also allows the transmembrane proteins contained in the vesicle membrane to be incorporated into the cell membrane, although such membrane protein trafficking is more characteristic of Ca 2+ -independent, constitutive exocytosis. Detailed Description In synapses, neuromuscular junctions, and endocrine cells, fast Ca 2+ -triggered exocytosis of a neurotransmitter or hormone-containing vesicle occurs primarily through the interaction of the so-called SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins spanning the synaptic and vesicle membranes with specific isoforms of the Ca 2+ -sensitive protein synaptotagmin and with involvement of other control proteins such as complexins (Jahn and Fasshauer 2012). Despite highly specialized morphology, a similar exocytosis-triggering mecha-nism is found at most high-throughput ribbon sensory synapses (Cho and von Gersdorff 2012; Sterling and Matthews 2005), except for cochlear hair cells which may differ in both their molecular exocytosis machinery and Ca 2+ sensitivity (Nouvian et al. 2011) and where exocytosis may require nonneuronal isoforms of synaptotagmin (Johnson et al. 2010) or a different Ca 2+ sensor, otoferlin (Pangrsic et al. 2012; Roux et al. 2006). The mechanism of exocytosis of hormone-containing large dense-core vesicles in endocrine cells is very similar to the mechanisms of neurotransmitter vesicle release (Chow et al. 1992; Voets 2000), but is believed to proceed at a somewhat slower rate due to less tight morphology of the release site and more lose coupling between voltage-dependent calcium channels and release-ready vesicles (Verhage and Toonen 2007; Wu et al. 2009). However, this distinction may be specific to only certain subclasses of endocrine cells, since a close channel-vesicle coupling characteristic of that in neurons has been found in pancreatic beta cells (Barg et al. 2001).