Synaptic transmission relies on spatially restricted and mechanistically regulated release of neurotransmitter. What seems like an obvious statement to make translates into cell biological questions of great importance: How is it brought about that SVs, the 50 nm-diameter lipid-bounded organelles that store neurotransmitter, are accumulated selectively at sites of neurotransmitter release, the so-called active zones? What mechanisms restrict their exocytic fusion, the event underlying neurotransmitter release, to these sites? Which molecular mechanisms account for the regulation of kinetics, amount, mode, and probability of neurotransmitter release at a given synapse, i.e. events that are thought to underlie conversion of synaptic transmission into information? Current notions hold that a network of cytoplasmic proteins that we have termed the cytomatrix assembled at the active zones (CAZ)1, which is a characteristic and specific feature of neurotransmitter release sites, plays a central role in the functional organization of synapses and may in fact mediate most of the above events.

Other chapters in this book deal with questions as to how the timing and the site of active zone formation are determined, and what extracellular and intra-cellular signals are involved in these events. In this chapter, we focus on questions as to how the components of active zones are assembled to generate the molecular machinery of neurotransmitter release. To this end, we define the individual components and highlight their characteristics. Moreover, we describe recent advances suggesting that active zone components are transported to nascent active zones on the surface of specialized vesicles.

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