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Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.

In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or v- and t-SNAREs, was essential for vesicle docking. However, more recently, it has been shown that vesicle docking can also occur without SNAREs. Additionally, two soluble proteins, N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment proteins (SNAP), bind to the SNARE complex to facilitate fusion.

The v-and t-SNAREs partially fuse in the priming process, forming a fusion-ready state. The protein complexin (Cpx) clamps the SNAREs and holds the vesicles in this partially fused state to prevent premature exocytosis. Vesicular membrane fusion begins when a stimulus, such as an action potential at the axonal terminal of a neuron, opens up a calcium channel, and calcium enters the cell. A total of five calcium ions bind to each synaptotagmin (Syt) – a vesicular membrane protein on either side of the vesicle. Calcium-bound Syt releases the Cpx clamp from the SNARE complexes and opens up the fusion pore to release the neurotransmitter. After fusion, NSF and SNAP proteins disassemble SNARE complexes for recycling.

Bacterial neurotoxins, such as botulinum from Clostridium botulinum or tetanus from Clostridium tetani, can inhibit secretory vesicle fusion by damaging the SNARE proteins, which prevents the fusion of secretory vesicles with the neuronal plasma membrane. As neurotransmitters are not released, action potentials are not generated, causing paralysis of muscles, and in some cases, death.

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