Figure 1.

The synaptic vesicle cycle and the roles of Hsc70, Auxilin, and Hsp110. The cycle begins with synaptic vesicle fusion and release of neurotransmitter. Assembly/adaptor proteins then bind to the synaptic vesicle membrane proteins and phosphoinositides, and recruit clathrin; leading to membrane invagination and subsequent vesicle scission by dynamin (green spheres), followed by binding of auxilin, which recruits Hsc70^*ATP (orange spheres) to the vesicle coat. The boxed region of the coated vesicle is expanded to show how Hsc70 binds to the flexible C-terminal tails that emerge from the helical tripod that is positioned under each vertex of the clathrin coat. Hsc70-driven disassembly (uncoating) of the coat follows, resulting in stable Hsc70^*ADP:Clathrin complexes. Hsp110 binding then induces ADP to ATP exchange and dissociation of the Hsp110:Hsc70:Clathrin complex.