Synaptotagmins 1 and 2 as mediators of rapid exocytosis at nerve terminals: The dyad hypothesis

• The dyad model proposes a novel mechanism for the regulation of exocytosis.
• It envisions that synaptotagmin molecules catalyze membrane fusion.
• This model is simpler and more-robust than SNARE models of exocytosis.
• The dyad model makes explicit predictions about the role of synaptotagmins.

The dyad model was developed to explain the extremely rapid kinetics of synaptic vesicle exocytosis. In contrast to most hypotheses which invoke interactions among synaptotagmins, SNAREs and other regulatory molecules, the dyad model features a quartet of synaptotagmins arrayed at the synaptic vesicle–plasma membrane interface. Ca2+-triggered movements of these synaptotagmins initiate a sequence of events culminating in the fusion of the vesicular and plasma membranes. The relative simplicity of this model and its amenability to empirical testing provide a useful template for future investigations of the molecular events underlying the exocytotic cascade.