Molecular organization and plasticity of the cytomatrix at the active zone

Regulated neurotransmitter release from presynaptic boutons is crucial for the functioning of chemical synapses, what in turn governs the functional performance of the nervous system. Release occurs at the active zone (AZ), a specialized region of the presynaptic plasma membrane that is defined by a unique and complex meshwork of proteins - the cytomatrix at the AZ (CAZ). Important functions of CAZ proteins include recruitment, docking and priming of synaptic vesicles as well as appropriate localization of voltage-gated calcium channels near vesicle docking sites. We will discuss recent progress in the understanding of the topological localization and the molecular functions of characteristic CAZ proteins as well as emerging molecular mechanisms underlying presynaptic plasticity that involve significant structural CAZ remodeling.

► A complex proteinous cytomatrix, the CAZ, organizes presynaptic transmitter release. ► Topological localization of CAZ proteins relative to presynaptic specializations. ► Control of calcium channel positioning relative to release sites. ► Organization of SV clusters and actin cytoskeleton by the CAZ. ► Molecular remodeling of the CAZ during synaptic plasticity.