Synaptotagmins

Introduction of Synaptotagmins

Synaptotagmins (SYTs) are a class of Synaptotagmins proteins, which play a key role in regulating membrane transport and exocrine of synaptic vesicles. A lot of members of the synaptotagmin family (17 isoforms) have been discovered, most of which are leading candidates to serve as the Ca²⁺ sensors that trigger neurotransmitter release. As the best-characterized isoform, synaptotagmin I (SYT1) is the most abundant Ca²⁺-binding protein on secretory organelles.

Structure of Synaptotagmins

SYTs consist of a short N-terminal transmembrane (TM) domain, a variable linker domain, and two C-terminal C2 domains (C2A and C2B). C2 domain containing 130-140 amino acid residues forms a highly conserved sequence motif that constitutes a stable eight-stranded β-sandwich with flexible loops emerging from the top and bottom. C2 domains are proposed to be Ca²⁺-sensing and Ca²⁺-binding structures to mediate Ca²⁺-dependent synaptic vesicle membrane fusion.

Fig.1 Structure of synaptotagmin.

Based on the sequences and properties of synaptotagmins, different vertebrate synaptotagmins can be grouped into 6 classes for better understanding the expression and function of synaptotagmins.

Table.1 Properties of synaptotagmins. (Südhof, 2002)

Function of Synaptotagmins

Synaptotagmins are well-established primary Ca²⁺ sensors to initiate presynaptic vesicular exocytosis and neurotransmitter release. Generally speaking, Ca²⁺ triggers the partial penetration of the Ca²⁺-binding loops of the C2 domains of synaptotagmin into lipid bilayers with very rapid kinetics, which might pull bilayers together to facilitate vesicle fusion and neuronal exocytosis. Moreover, synaptotagmin C2 domains interact directly with the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) complex to form the core of a conserved membrane fusion machine. These interactions might facilitate the assembly of SNARE complexes to accelerate fusion. Therefore, synaptotagmin is thought to play an important role in the docking fusion between synaptic vesicles and plasma membranes, such as the release of neurotransmitters.

Fig.2 Synaptotagmin-1 induces membrane fusion and vesicular exocytosis.

Synaptotagmins play critical roles in the docking, priming, and fusion steps of exocytosis, as well as the presynaptic neurotransmitter release. To better understand and study the synaptic endocytosis and neurotransmitter release, Creative Biolabs now provides a variety of antibodies, proteins, agonists/antagonists, toxins against various targets in the exocytosis pathway to meet our clients’ requirements. If the premade product cannot meet your needs, we also provide one-stop customized development services to best match your demands. If you are interested in our services and products, please do not hesitate to contact us for more detailed information.

Reference

1. Südhof, T. C. Synaptotagmins: why so many? Journal of biological chemistry. 2002, 277(10): 7629-7632.