Cellular membrane fusion involves the formation of a four-helix bundle with contributions from vesicle and target membrane SNARE (soluble NSF attachment protein receptor) proteins. SNAREs constitute the minimal fusion machinery and can promote the fusion of liposomes. Pobbati et al. dissected the SNARE assembly process in greater detail. In vitro experiments with liposomes showed that SNARE assembly was initiated at the N-terminal region of the four-helix bundle and that was sufficient to drive rapid liposome fusion. Giraudo et al. used a system in which SNARE proteins, which are normally expressed on intracellular membranes, are "flipped" so that they are exposed at the cell surface. Cells expressing such flipped SNARES fuse spontaneously. By introducing a fusion clamp (complexin) and a calcium sensor (synaptotagmin), cell-cell fusion can be regulated by calcium in a comparable way to the regulation seen during neurotransmitter release.