Starting my lab When I started my laboratory in 1986 at the University of Texas Southwestern in Dallas, exquisite electrophysiological studies had already characterized neurotransmitter release in detail. These studies showed that calcium triggers release within a few hundred microseconds, exhibits amazing plasticity and displays a nonlinear dependence on calcium. However, aside from calcium, not a single molecule important for release had been identified. Genetic screens by Sidney Brenner, Randy Scheckman and their colleagues had isolated gene mutations that disrupt synaptic transmission in Caenorhabditis elegans or impair the secretory pathway in yeast, but the function of the corresponding proteins were unknown. In pioneering work, Rothman performed in vitro membrane fusion assays using non-neuronal cells, but the molecular mechanisms involved in these fusion reactions were unclear. The lack of knowledge about how synaptic vesicle fusion happens and how such fusion is controlled by calcium intrigued me and led me to search for molecular mechanisms. We chose a simple approach: to isolate and clone all of the major proteins present in presynaptic terminals. Initially, in collaboration with Reinhard Jahn, we focused on synaptic vesicles because they could be isolated at high yield and purity. Later on, we expanded this approach to the presynaptic active zone and plasma membrane. The goal was to achieve a molecular catalog of protein components of the presynaptic terminal as a starting point for a functional dissection. For over a decade, we purified and cloned a series of major synaptic proteins—among others, synaptophysin, synaptobrevin,