Science 336, 1581–1584 (2012)

Credit: © 2012 AAAS

In neurons, neurotransmitter vesicles release their cargo at the synapse, a necessary step in the propagation of nerve signals. For this, the vesicles must first dock near release sites and then fuse with the presynaptic membrane — the membrane that faces the receiving cell. This process is known to be mediated by the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family of membrane-bound proteins, each consisting of four-helix bundles that can assemble into complexes in a zipper-like manner. However, how the assembly of SNARE complexes in apposed lipid bilayers leads to docking, fusion intermediates and ultimately fusion of the vesicles remains unclear. Now, Javier Hernandez and colleagues perturbed the assembly of purified SNAREs reconstituted in liposomes to be able to arrest membrane-fusion intermediates. Their observations lead them to conclude that bilayer docking results from partial SNARE zippering, and that further zippering pulls the bilayers tighter, straining the lipids at the edges of an extended docking area. The researchers suggest that such an extended docking configuration is an intermediate state that initiates fusion.