SNAREpins are functionally resistant to disruption by NSF and alpha SNAP

SNARE (SNAP [soluble NSF (N-ethylmaleimide-sensitive fusion protein) attach ment protein] receptor) proteins are required for many fusion processes, an d recent studies of isolated SNARE proteins reveal that they are inherently capable of fusing lipid bilayers. Cis-SNARE complexes (formed when vesicle SNAREs [v-SNAREs] and target membrane SNAREs [t-SNAREs] combine in the sam e membrane) are disrupted by the action of the abundant cytoplasmic ATPase NSE which is necessary to maintain a supply of uncombined v- and t-SNAREs f or fusion in cells. Fusion is mediated by these same SNARE proteins, formin g trans-SNARE complexes between membranes. This raises an important questio n: why doesn't NSF disrupt these SNARE complexes as well, preventing fusion from occurring at all? Here, we report several lines of evidence that demo nstrate that SNAREpins (trans-SNARE complexes) are in fact functionally res istant to NSF, and they become so at the moment they form and commit to fus ion. This elegant design allows fusion to proceed locally in the face of an overall environment that massively favors SNARE disruption.