TY - JOUR TI - Fusion of tethered membranes can be driven by Sec18/NSF and Sec17/αSNAP without HOPS AU - Song, Hongki AU - Wickner, William T A2 - Linstedt, Adam A2 - Pfeffer, Suzanne R A2 - Merz, Alexey J VL - 10 PY - 2021 DA - 2021/10/26 SP - e73240 C1 - eLife 2021;10:e73240 DO - 10.7554/eLife.73240 UR - https://doi.org/10.7554/eLife.73240 AB - Yeast vacuolar membrane fusion has been reconstituted with R, Qa, Qb, and Qc-family SNAREs, Sec17/αSNAP, Sec18/NSF, and the hexameric HOPS complex. HOPS tethers membranes and catalyzes SNARE assembly into RQaQbQc trans-complexes which zipper through their SNARE domains to promote fusion. Previously, we demonstrated that Sec17 and Sec18 can bypass the requirement of complete zippering for fusion (Song et al., 2021), but it has been unclear whether this activity of Sec17 and Sec18 is directly coupled to HOPS. HOPS can be replaced for fusion by a synthetic tether when the three Q-SNAREs are pre-assembled. We now report that fusion intermediates with arrested SNARE zippering, formed with a synthetic tether but without HOPS, support Sec17/Sec18-triggered fusion. This zippering-bypass fusion is thus a direct result of Sec17 and Sec18 interactions: with each other, with the platform of partially zippered SNAREs, and with the apposed tethered membranes. As these fusion elements are shared among all exocytic and endocytic traffic, Sec17 and Sec18 may have a general role in directly promoting fusion. KW - membrane fusion KW - yeast vacuole KW - SNAREs KW - HOPS KW - Sec17 KW - Sec18 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -