An important goal of our laboratory is to elucidate mechanisms in the biogenesis and traffic of synaptic vesicles at neuronal synapses, with emphasis on the processes that mediate their reformation by endocytic recycling after each cycle of secretion. We use a variety of complementary approaches that include reconstitution experiments with purified endocytic proteins and lipid membranes, broken cell preparations, intact cells, model synapses and genetically modified mice. With these studies we hope not only to improve knowledge of synaptic transmission but also to advance the understanding of fundamental mechanisms in endocytosis. In my talk I will discuss the role of the GTPase dynamin, a protein implicated in the fission reaction of endocytosis, and the impact of the lack of dynamin on cell structure and physiology. We have generated KO mice for each of the three dynamin isoforms. These mice, as well as cells derived from them, allow us to study the fundamental function of dynamin as well as isoforms specific functions. Surprisingly, cells without any dynamin live, although they fail to proliferate and they display major alterations in the structure of the cell surface. I will also discuss the function of dynamin binding partners with curvature generating and curvature sensing properties (proteins with BAR and F-BAR domains), and the mechanisms through which these proteins deform membranes (Roux et al. Nature 441: 528-531; Ferguson et al. Science 316: 570-574; Frost et al. Cell 132:807-817).