Complexins
Introduction of Complexins
Complexin (Cpx), which is expressed mainly in the nervous system, plays a major role in governing SNARE assembly during vesicle fusion. It binds to the SNARE protein complex with a high affinity to regulate both spontaneous and calcium-triggered neurotransmitter release in all synapses. Complexin I to IV (Cpx I to IV) has been identified. Cpx I, II, and III are shown to be expressed in the brain and the retina, whereas Cpx IV is present only at retinal ribbon synapses. Complexins are either facilitators or inhibitors of vesicle exocytosis, functioning to promote evoked neurotransmitter release following an action potential, or acting as fusion clamps to inhibit spontaneous vesicle fusion in the absence of Ca2+.
Structure of Complexins
As a small highly charged cytosolic protein, complexin is hydrophilic with rich glutamic acid and lysine residues. Complexin I consists of four domains: an N terminal domain (NTD, amino acid 1-32), an accessory alpha helix (AH, amino acid 33-47), a central alpha helix (CH, amino acid 48-70), and a carboxy terminal domain (CTD, amino acid 71-134). Amongst, CH domain binds with the SNARE complex that is a prerequisite for all complexin actions. These Cpx domains coordinately potentiate the efficacy of the synchronous exocytotic process.
Fig.1 Structure of complexin-1. (Trimbuch, 2016)
Based on different domains of complexin, comprehensive structure-function analysis has been crucial for understanding the role of complexin in regulating evoked and spontaneous release.
Table.1 Structure-function analysis of complexin domains in different experimental settings. (Trimbuch, 2016)
Function of Complexins
Dependent upon the synaptic activity, complexin carries dual functions with both inhibitory and facilitatory roles in regulating vesicle fusogenicity.
- Acting to Inhibit Fusion
- Acting to Promote Fusion
Inhibition of fusion is necessary to prevent spontaneous exocytosis of vesicles into the synapse. The possible mechanism may involve inhibitory binding of complexin to the assembling SNARE complex. The C-terminal domain of complexin is believed to be responsible for this inhibitory function. In addition, low levels of calcium are thought to induce a comparatively stronger clamping and inhibitory effect of complexin on spontaneous vesicle release.
Independent of the clamping functionality, complexin might exert a fusion-promoting function when a stimulus is transmitted to the synapse. N-terminus of complexin accelerates the kinetics of primed vesicle fusion. This activation pathway is mediated by synaptotagmin-10.
Complexins bind the SNARE complex and regulate the evoked and spontaneous synaptic transmissions. It usually inhibits spontaneous release and promotes evoked transmission to maintain nervous system homeostasis. Creative Biolabs now provides a variety of antibodies, proteins, agonists/antagonists, toxins against various targets in the exocytosis pathway to meet our clients’ requirements. We also provide one-stop customized development services for our clients. If you are interested in our services and products, please do not hesitate to contact us for more detailed information.
Reference
- Trimbuch, T.; Rosenmund, C. Should I stop or should I go? The role of complexin in neurotransmitter release. Nature Reviews Neuroscience. 2016, 17(2): 118.
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