Figure 2.

Scheme of an excitatory synapse. Pre-synaptic proteins are organized in a functional complex, playing different roles in vesicular exocytosis. Membrane fusion is a key process for neurotransmitter release. SNARE proteins are the central constituents of the eukaryotic fusion machinery that triggers the fusion of synaptic vesicles (SV), whose membranes contains synaptotagmin 1 (Syt1) and synaptobrevin (VAMP-2), with the plasma membrane [134,135]. The exocytosis stages comprise a docking step, which occurs when the synaptic vesicle comes into contact with the presynaptic plasma membrane named active zone. VAMP-2 then assembles with syntaxin (Stx1a) and SNAP-25 to form a core trans-SNARE complex. Next, the priming step makes the vesicle competent for fusion and fusion pore formation [136]. Finally, the fusion pore opening is followed by fusion pore expansion leading to release of the vesicle contents with the neurotransmitter [137]. Two active-zone proteins, Munc-18 and Munc-13, are key regulators of neurotransmitter release due to their action on the assembly of the SNARE complex, composed by Stx1a, SNAP-25, and VAMP-2 [138,139]. Stages of exocytosis are as follows. (1) Docking: the synaptic vesicle and the plasma membrane are brought into contact. (2) Priming: this step renders the vesicle as being fusion-competent and enables fusion pore formation. (3) Fusion pore opening and release or exchange of the vesicle content.