SNARE proteins mediate lipid bilayer fusion.

Lipid bilayers compartmentalize eukaryotic cells into distinct organelles. This compartmentalization allows for specialization of diverse cellular processes, from DNA polymerization to zymogen proteolysis. While the specific complement of proteins present in each organelle defines its function, there is a dynamic flux between these organelles. The selective transport of proteins between organelles is the central process in the organization of membrane compartments. This process is largely mediated by the budding of transport vesicles from a donor compartment followed by the vectoral trafficking to and fusion with an acceptor compartment. Over the last several years considerable effort has been exerted to uncover the molecular mechanisms underlying this process. A set of protein families known as SNAREs [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptors] is at the crux of vesicle docking and/or fusion. Members of these families reside on transport vesicles (v-SNARES) and on target membranes (t-SNAREs) and bind to each other. While previously implicated in conferring specificity to vesicle trafficking, more recent studies have demonstrated that these proteins also may mediate the fusion process itself. In two papers in this issue of PNAS, Rothman and colleagues (1, 2) demonstrate that liposomes reconstituted with only v- and t-SNAREs can fuse and mix luminal contents with reasonably physiological kinetics. These results further implicate SNAREs as the core fusion machinery for intracellular vesicle trafficking.