N-terminal SNARE complex binding domain of the complexin family of SNARE regulators
Complexins (CPXs) are small, cytosolic proteins that bind to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex to regulate synaptic vesicle exocytosis. There are four CPX isoforms: complexin I/synaphin-2, complexin II/synaphin-1, complexin III and complexin IV. CPXs I and II are highly homologous hydrophilic proteins that are enriched in neurons where they colocalize with syntaxin and SNAP25. They regulate the sequential interactions of alpha-SNAP and synaptotagmins with the SNAP receptor during exocytosis. CPXs III and IV are the only CPX isoforms present in retinal ribbon synapses. In addition, CPXs III and IV carry an extension with a functional CAAX-box farnesylation site that is absent in CPXs I and II. Their C-terminal farnesylation regulates their synaptic targeting and modulatory function in transmitter release. They may contribute to the unique release efficacy of retinal sensory neurons. CPXs III and IV can functionally replace CPXs I and II. Most of the invertebrate CPXs are more similar to CPXs I and II than to CPXs III and IV. This model corresponds to the N-terminal region of CPX that is responsible for SNARE complex binding.
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