Maintaining the active zone: Demand, supply and disposal of core active zone proteins

•Cytoskeleton associated with the Active Zone proteins are core presynaptic elements.•Half-lives of CAZ proteins (a few days) are much shorter than synapse lifespans.•Findings concerning CAZ protein replenishment and degradation are reviewed.•Different studies and approaches often result in inconsistent conclusions.•Further progress requires consideration of context and spatiotemporal constraints. Chemical synapses are sites of cell–cell contact specialized for transmission of signals between neurons and their respective targets. Neurotransmission occurs through the secretion of neurotransmitters at specialized presynaptic membrane regions known as Active Zones (AZs). AZ composition and function are now characterized quite well. Much less is known, however, on the manners by which these unique specializations are maintained for weeks, months, and presumably years. Here we focus on core AZ components that make up the Cytoskeleton associated with the AZ (CAZ) – their lifetimes, their supply and their disposal. We describe recent findings on CAZ molecule turnover rates, on the synthesis and trafficking of CAZ molecules to synapses and on the manners by which they are degraded. We highlight converging findings, point to discrepancies, in particular related to temporal and spatial constraints, and try to reconcile these, where possible, by offering more inclusive interpretations.