Sec17 (α-SNAP) and an SM-tethering complex regulate the outcome of SNARE zippering in vitro and in vivo

Matthew L. Schwartz, Daniel P. Nickerson, Braden T. Lobingier, Rachael L. Plemel, Mengtong Duan, Cortney G. Angers, Michael Zick, Alexey J. Merz

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere27396
JournaleLife
Volume6
DOIs
StatePublished - Sep 19 2017
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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