The complex chromatin-based genomic regulatory system controlling developmental gene expression in complex bilaterians predates the evolution of morphological complexity and may have been a prerequisite for the evolution of the first simple multicellular animals.
Building on previous work (Diao et al., 2012), we show that the mechanism by which complexin suppresses spontaneous fusion is distinct from the mechanism by which it synchronizes Ca2+-triggered fusion.
Cooperative action of synaptotagmin and complexin is needed to arrest all SNARE complexes on a vesicle, and the reversal of the synaptotagmin clamp is sufficient to achieve fast, Ca2+-synchronized fusion.
Isothermal titration calorimetry experiments clarify apparently discrepant results described previously and show that N-terminal sequences of complexin bind to SNARE complexes containing C-terminally truncated synaptobrevin when they include the syntaxin-1 juxtamembrane region.
Challenging a widespread model, biophysical and electrophysiological experiments suggest a new mechanism whereby complexins inhibit neurotransmitter release through electrostatic repulsion between their accessory helix and the membranes.