High resolution

Module 4: Figure Ca2+-induced membrane fusion

Exocytotic machinery: a hypothetical mechanism for Ca2+-induced membrane fusion.

The major proteins that function in exocytosis are the vesicle soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor (v-SNARE) synaptobrevin and the target SNAREs (t-SNAREs) syntaxin and 25 kDa synaptosome-associated protein (SNAP-25). These three SNAREs interact with each other in the docked state (left) to form a ternary complex. This complex may be prevented from interacting further by regulatory proteins such as the Ca2+-sensitive proteins synaptotagmin I/II. A single voltage-operated channel (VOC), a member of the CaV2 family of N-type, P/Q-type and R-type channels, is anchored to syntaxin or SNAP-25 and opens in response to depolarization to introduce a pulse of trigger Ca2+ that acts through the synaptotagmins to enable the SNAREs to drive the two membranes to fuse with each other. These synaptotagmins have two adjacent C2 domains (C2A and C2B), which have Ca2+-binding pockets with the low affinities (40 μM to 1 mM) necessary to respond to the high levels of Ca2+ found in the microdomains surrounding the vesicles. The site where the SNAREs interact with the CaV2 family of VOCs is shown in Module 3: Figure CaV2 channel family.