TY - JOUR
T1 - Sec17 (α-SNAP) and an SM-tethering complex regulate the outcome of SNARE zippering in vitro and in vivo
AU - Schwartz, Matthew L.
AU - Nickerson, Daniel P.
AU - Lobingier, Braden T.
AU - Plemel, Rachael L.
AU - Duan, Mengtong
AU - Angers, Cortney G.
AU - Zick, Michael
AU - Merz, Alexey J.
N1 - Funding Information:
We thank members of our groups for insightful discussions and comments on the manuscript, W Wickner for hosting AJM to learn the liposome fusion system and for provision of reagents, and G Odorizzi and R Scheckman for sharing yeast strains. The Merz lab’s work on membrane fusion is supported by NIH-NIGMS GM077349; the Wickner lab’s, by GM023377.
Publisher Copyright:
© Schwartz et al.
PY - 2017/9/19
Y1 - 2017/9/19
N2 - Zippering of SNARE complexes spanning docked membranes is essential for most intracellular fusion events. Here, we explore how SNARE regulators operate on discrete zippering states. The formation of a metastable trans-complex, catalyzed by HOPS and its SM subunit Vps33, is followed by subsequent zippering transitions that increase the probability of fusion. Operating independently of Sec18 (NSF) catalysis, Sec17 (α-SNAP) either inhibits or stimulates SNAREmediated fusion. If HOPS or Vps33 are absent, Sec17 inhibits fusion at an early stage. Thus, Vps33/HOPS promotes productive SNARE assembly in the presence of otherwise inhibitory Sec17. Once SNAREs are partially zipped, Sec17 promotes fusion in either the presence or absence of HOPS, but with faster kinetics when HOPS is absent, suggesting that ejection of the SM is a rate-limiting step.
AB - Zippering of SNARE complexes spanning docked membranes is essential for most intracellular fusion events. Here, we explore how SNARE regulators operate on discrete zippering states. The formation of a metastable trans-complex, catalyzed by HOPS and its SM subunit Vps33, is followed by subsequent zippering transitions that increase the probability of fusion. Operating independently of Sec18 (NSF) catalysis, Sec17 (α-SNAP) either inhibits or stimulates SNAREmediated fusion. If HOPS or Vps33 are absent, Sec17 inhibits fusion at an early stage. Thus, Vps33/HOPS promotes productive SNARE assembly in the presence of otherwise inhibitory Sec17. Once SNAREs are partially zipped, Sec17 promotes fusion in either the presence or absence of HOPS, but with faster kinetics when HOPS is absent, suggesting that ejection of the SM is a rate-limiting step.
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U2 - 10.7554/eLife.27396
DO - 10.7554/eLife.27396
M3 - Article
C2 - 28925353
AN - SCOPUS:85032932166
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e27396
ER -