Calcium triggers an intramolecular association of the C2 domains in synaptotagmin

Synaptotagmin I is a critical component of the synaptic machinery that senses calcium influx and triggers synaptic: vesicle fusion and neurotransmitter release. Fluorescence resonance energy transfer studies conducted on synaptotagmin demonstrate that calcium concentrations required for fusion induce a conformational change (EC50 approximate to 3 mM) that brings the two calcium-binding C2 domains in synaptotagmin closer together. Analytical ultracentrifugation studies reveal that synaptotagmin is monomeric under these conditions, indicating that this calcium-triggered association between the C2 domains is intramolecular, rather than intermolecular. These results suggest a mechanism for synaptotagmin function at the presynaptic plasma membrane that involves the self-association of C2 domains.