organisms, mutations to complexin were linked to dramatic increases in spontaneous exocytosis rates. A possible mechanism for how complexin mechanistically anchors vesicles to prevent fusion involves inhibitory binding to the assembling SNARE complex. It is suggested that complexin's N-terminal alpha-helix domain incorporates itself into the SNARE complex helix bundle and prevents zippering of the assembly. In contrast to this, another hypothesis is that complexin, independent of synaptotagmin interactions, cross-links with SNARE complexes in a zig-zag array. Recent data supports the former, that synaptotagmin plays a role in causing a conformational change in SNARE interactions similar to the change caused by calcium. This binding of calcium-bound synaptotagmin creates an interaction that releases the fusion clamp of complexin, causing membrane fusion and exocytosis to occur. 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. This pathway is mediated by synaptotagmin-10 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 , , , See also Synaptotagmin References Proteins