Mechanisms controlling assembly and plasticity of presynaptic active zone scaffolds

•Active zone scaffold size scales with synaptic vesicle release probability.•The dynamics of material flux and incorporation at the AZ control AZ size.•Axonal transport, local exchange, localization mechanisms control scaffold plasticity.

Cognitive processes including memory formation and learning rely on a precise, local and dynamic control of synapse functionality executed by molecular changes within both presynaptic and postsynaptic compartments. Recently, the size of the presynaptic active zone scaffold, a cluster of large multi-domain proteins decorating the presynaptic plasma membrane, was found to directly scale with the action potential evoked release of synaptic vesicles. The challenge now is to constitute an integrated picture of how long-range axonal transport, local exchange and localization mechanisms at the scaffold and degradation processes are integrated to allow for dynamic and controlled scaffold rearrangements. Here we discuss findings from multiple model systems emphasizing both short-term and long-term regulations of active zone composition and function.

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