Nerve Terminals

Active zones may be considered as central components of a larger machinery designed to guarantee controlled neurotransmitter release and local maintenance of the contributing components. These components are (a) SVs, (b) active zones, and (c) periactive zones. Clusters of SVs are selectively accumulated close to active zones. Functionally, these SVs can be divided into several pools, depending on their responsiveness to stimulation of transmitter release2-4. Exocytic release of neurotransmitter occurs from SVs fusing with the active zone plasma membrane and involves formation of a complex between the SNARE-proteins VAMP, a transmembrane protein of SVs, and syntaxin and SNAP25 in the plasma membrane2,5. Not all SVs fuse with the same probability upon nerve stimulation. Acquisition of fusion competence is thought to be controlled critically by proteins of the CAZ.

At some synapses, the active zone does not only release neurotransmitter, but also regenerates fused or fusing SVs locally by clathrin-independent mechanisms termed kiss-and-run and kiss-and-stay2,3,6. Usually, synapses are capable of retrieving fused SVs by clathrin-mediated endocytosis, which occurs at the regions peripheral to the active zone, termed periactive zones2,7. Such SVs are locally routed back into the SV cloud. CAZ proteins are likely to be involved in linking the exocytic and endocytic zones in presynaptic boutons8. As discussed below a major question regarding active zone assembly turns out to be: To what extent are the components of the release machinery recruited simultaneously to nascent synapses?

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