Ca2+ and lipid control of vesicle fusion in ß-cells and neurons. Insulin and neurotransmitters are released from β-cells and neurons, respectively, by the timed, Ca2+-dependent exocytosis of vesicles, requiring the fusion of lipidic vesicle- and plasma membranes. The composition of the fusing membranes is likely a key factor in this reaction, but relatively little is known how lipid signaling, together with Ca2+ and proteins, controls exocytosis. In this project we will identify lipid-interacting proteins and, by fast light-switching of lipid concentrations, study how lipid signaling affects intracellular Ca2+, exocytosis rates and protein localization in both systems. Experiments will be combined with kinetic mathematical modeling to build a theoretical framework of protein, Ca2+ and lipid interactions driving exocytosis in both systems.