Complexin

Structure and Binding

Complexin is a small highly charged cytosolic protein that is hydrophilic, rich in glutamic acid and lysine residues. Complexin's central region (amino acids 48–70) binds to the SNARE core as an anti-parallel α-helix, which attaches complexin to the SNARE complex. It interacts selectively with the ternary SNARE complex but not with monomeric SNARE proteins. Complexin binds to the groove between the synaptobrevin and syntaxin helices. Complexin stabilizes the C-terminal part of the SNARE complex.

Function

Complexin acts as a positive regulator of synaptic vesicle exocytosis, and binds selectively to the neuronal SNARE complex. Complexin has a two-fold function in that it can act as either a promoter or an inhibitor of vesicle fusion. This dual-functionality is dependent upon synaptic activity such as a depolarizing stimulus arriving at the synapse. By acting as a fusion clamp in inhibiting fusion, and a promoter during depolarization, complexin concentration levels regulate vesicle pool size such as that of the ready releasable pool, important for short term response changes.{{Cite journal

Complexin Acts to Inhibit Fusion - Fusion Clamping

Inhibition of fusion is necessary to prevent spontaneous exocytosis of vesicles into the synapse. If a clamp does not hold synaptic vesicle pools stable and inhibit them from fusing, the potential for spontaneous firing and depletion of the vesicle pool is much greater. It is believed that the C-terminal domain of complexin is responsible for this inhibitory function.{{Cite journal

A possible mechanism for how complexin mechanistically anchors vesicles to prevent fusion involves inhibitory binding to the assembling SNARE complex.{{Cite journal

• Calcium Effects In low levels of calcium, complexin has a comparatively stronger clamping and inhibitory effect on spontaneous vesicle release. This is thought to be countered by synaptotagmin at increasing calcium levels, as the activity of synaptotagmin increases, providing more energy to remove the clamping effect of complexin.

Complexin Acts to Promote Fusion

Complexin can also promote fusion when a stimulus is transmitted to the synapse. Independent of its clamping functionality (such as when the C-terminal of complexin is knocked out), complexin can still function as an exocytosis promoter.{{Cite journal

Association with Synaptotagmin

Complexin knockdown experiments have been linked to Synaptotagmin-1 and -10 dependent exocytosis. Both Synaptotagmin proteins seem reliant on a complexin co-factor, indicating complexin's importance across the synaptotagmin family.

Genes

• , , ,

References

References

1. Krishnakumar, Shyam. (August 2011). "A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion". Nature Structural & Molecular Biology.
2. (2002). "Action of complexin on SNARE complex.". J Biol Chem.
3. (1995). "Synaphin: a protein associated with the docking/fusion complex in presynaptic terminals.". Biochem Biophys Res Commun.