Unfortunately, length restrictions preclude a discussion of

many important papers and issues in the field, and I apologize for the many omissions I am bound to commit. Despite significant progress, much about active zones remains unknown, and I will at the end MLN0128 of each section briefly discuss open questions and major challenges. Synaptic vesicle exocytosis likely emerged evolutionarily from nonsynaptic forms of neurosecretion that are observed in primitive animals such as trichoplax or nomastella. Although these animals lack morphologically identifiable synapses, they contain genes homologous to synaptotagmins and complexins that mediate the Ca2+-triggering of synaptic vesicle fusion. The emergence of synapses probably depended on the evolutionary construction of the active zone that

organizes the Ca2+-triggering of neurotransmitter secretion, and restricts it to a small membrane patch opposite to a cluster of postsynaptic receptors. Thus, active zones are a key component of what defines a synapse. In central synapses of vertebrates, active zones are disc-like structures Selleckchem Dabrafenib with a 0.2–0.5 μm diameter. Active zones are surrounded by a perisynaptic zone that is functionally an intrinsic part of a synapse. The perisynaptic zone is the site of synaptic vesicle endocytosis (Brodin and Shupliakov, 2006), contains transsynaptic cell-adhesion molecules such as cadherins (Uchida et al., 1996) and harbors presynaptic receptors such as endocannabinoid CB1 receptors that control neurotransmitter release (Nyíri et al., 2005). Different from the disc-shaped active zones of central synapses, neuromuscular junctions contain elongated active zones to which synaptic vesicles are attached like pearls on a string (Harlow et al., 2001). Moreover, some sensory neurons of vertebrates form specialized ribbon synapses that are characterized by a synaptic ribbon or body that is positioned

perpendicular to the plane much of the plasma membrane (Matthews and Fuchs, 2010). Evolutionarily, synaptic ribbons probably arose in vertebrates with the generation of RIBEYE, their major protein component that represents a fusion of a novel N-terminal domain encoded by a single large exon with another protein called CtBP2 (Schmitz et al., 2000). Ribbon synapses contain their characteristic synaptic ribbons in addition to standard active zones, and the ribbons appear to function as accelerators in the recruitment of vesicles for exocytosis (Matthews and Fuchs, 2010). Active zones of invertebrate synapses are similar to central vertebrate synapses, except for specializations such as the t bars in Drosophila that similar to synaptic ribbons appear to function in recruiting vesicles to active zones ( Kittel et al., 2006). In the present discussion, due to space constraints we will focus on the core components shared by all active zones as far known, and only refer to more specialized features in passing.