Abstract
Neuronal communication is tightly regulated in time and space. Following neuronal activation, an electrical signal triggers neurotransmitter (NT) release at the active zone. The process starts by the signal reaching the synapse followed by a fusion of the synaptic vesicle (SV) and diffusion of the released NT in the synaptic cleft. The NT then binds to the appropriate receptor and induces a membrane potential change at the target cell membrane. The entire process is controlled by a fairly small set of synaptic proteins, collectively called SYCONs. The biochemical features of SYCONs underlie the properties of NT release.SYCONs are characterized by their ability to detect and respond to changes in environmental signals. For example, consider synaptotagmin I (Syt1), a prototype of a protein family with over 20 gene and variants in mammals. Syt1 is a specific example of a multi-sensor device with a large repertoire of discrete states. Several of these states are stimulated by a local concentration of signaling molecules such as Ca2+. The ability of this protein to sense signaling molecules and to adopt multiple biochemical states is shared by other SYCONs such as the synapsins (Syns). Specific biochemical states of Syns determine the accessibility of SV for NT release. Each of these states is defined by a specific alternative spliced variant with a unique profile of phosphorylation modified sites.The plasticity of the synapse is a direct reflection of SYCON's multiple biochemical states. State transitions occurs in a wide range of time scales, and therefore these molecules need to cope with events that last milliseconds (i.e., exocytosis in fast responding synapses) and with events that can carry on for many minutes (i.e., organization of SV pools). We suggest that SYCONs are optimized throughout evolution as multi-sensor devices. A full repertoire of the switches leading to alternation of protein states and a detailed characterization of protein-protein network within the synapse is critical for the development of a dynamic model of synaptic transmission.
Highlights
The structure and function of the nerve terminal has been a topic of extensive research for many years [1,2]
We suggest that SYCONs are optimized throughout evolution as multi-sensor devices
A small set of proteins from the presynaptic site, collectively referred to as Synaptic control of neurotransmitter release protein (SYNCON) (Synaptic Control of Neurotransmitter release proteins) are characterized by the following features: Once we focus on proteins directly involved in the synaptic vesicle (SV) fusion event, we are left with few proteins of the exocytotic core: the SNAP receptors (SNARE) (VAMP, syntaxin and SNAP-25), their immediate associated protein synaptotagmin (Syt) and the voltage dependent Ca2+ channel (VDCC) [11]
Summary
The structure and function of the nerve terminal has been a topic of extensive research for many years [1,2]. A small set of proteins from the presynaptic site, collectively referred to as SYNCONs (Synaptic Control of Neurotransmitter release proteins) are characterized by the following features: Once we focus on proteins directly involved in the SV fusion event, we are left with few proteins of the exocytotic core (yet each may belong to a family of closely related proteins): the SNAREs (VAMP, syntaxin and SNAP-25), their immediate associated protein synaptotagmin (Syt) and the voltage dependent Ca2+ channel (VDCC) [11]. Synaptic proteins as information integrators To fully appreciate the potential of molecules such as Syt and Syns as 'coincidence detector devices', quantitative parameters on binding properties, on competition and affinities and on modification of the molecules under physiological setting are essential. The efficiency of vesicle fusion, fission and cell division is strongly dependent on the appropriate membrane curvature [58]
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