The Presynaptic Active Zone

Abstract

Neurotransmitters are released by synaptic vesicle exocytosis at the active zone of a presynaptic nerve terminal. In this review, I discuss the molecular composition and function of the active zone. Active zones are composed of an evolutionarily conserved protein complex containing as core constituents RIM, Munc13, RIM-BP, α-liprin, and ELKS proteins. This complex docks and primes synaptic vesicles for exocytosis, recruits Ca2+ channels to the site of exocytosis, and positions the active zone exactly opposite to post-synaptic specializations via transsynaptic cell-adhesion molecules. Moreover, this complex mediates short- and long-term plasticity in response to bursts of action potentials, thus critically contributing to the computational power of a synapse.

Numbers of presynaptic Ca 2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses

“…neurotransmitter release | active zone | calcium channel | release site | parallel fiber I n presynaptic terminals, the active zone (AZ) represents a highly specialized structure allowing the binding and Ca 2+ -dependent release of synaptic vesicles (SVs) (1). Fluctuation analysis of synaptic signals suggests the presence of one or several functional units per AZ (2,3).…”

“…In molecular terms, docking sites are thought to be composed of a multiprotein assembly including RIM, RIM-binding protein, Munc13, Munc18, and SNARE proteins (1,6,12). This protein complex interacts with presynaptic voltage-gated Ca 2+ channels (VGCCs) (1).…”

“…This protein complex interacts with presynaptic voltage-gated Ca 2+ channels (VGCCs) (1). Furthermore, the remarkably short duration of synaptic delay (13), as well as analysis of the inhibition of synaptic release by VGCC blockers or by slow-binding Ca 2+ buffers in certain synapses (reviews: refs.…”

Release of chemical transmitters from cell bodies and dendrites of nerve cells

“…At presynaptic nerve terminals short-term plasticity lasting for seconds, minutes or hours is evident as facilitation, depression and post-tetanic potentiation of release [9,10]. By contrast, long-term changes in the efficacy of transmission are caused for the most part by postsynaptic mechanisms, involving NMDA [11] and metabotropic receptors [12,13]. Release from neuronal cell bodies and dendrites gives rise to maintained transmitter concentrations in the extracellular spaces of not only near, but also distant neurons, glial cells and blood vessels [14].…”

Structural characterization of the Rabphilin-3A–SNAP25 interaction

“…Other important players are complexin, Munc18-1, Munc13, and a collection of proteins that share a common structural motif: the C2 domain (5,6). These domains are regulated by their ability to bind Ca 2+ , phospholipids, and protein interactions, endowing them with properties to fine-tune the wide variety of vesicle release modes (7). Nowadays, we have detailed information on many of the steps contributing to docking, priming, and fusion of these vesicles, but a clear picture on how these regulators contribute in each particular state still remains under debate, mainly due to the lack of high-resolution structural data.…”