
Project P10 will biochemically and structurally characterize the events corresponding to synaptic vesicle tethering at the active zone, involving Rab3 and its interacting partner Rim1. The ultimate goal is the in vitro reconstitution of the entire reaction cascade mediating synaptic vesicle exocytosis, starting with vesicle tethering and concluding with fusion pore dilation. In particular, we will image different steps to reveal how protein-protein and protein-lipid interactions control the formation of the metastable prefusion state, the approach of the two lipid bilayers and membrane shape. In addition, we aim to capture and visualize Ca2+-triggered structures, such as hemifusion intermediates and fusion pores.