Sec17 (α-SNAP) and an SM-tethering complex regulate the outcome of SNARE zippering in vitro and in vivo.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28925353.
- Also identified by DOI 10.7554/eLife.27396 and PMC identifier 5643095.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 SNARE-mediated 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.
Medical subject headings
- Intracellular Membranes
- Membrane Fusion
- SNARE Proteins
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins
- Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
- Vesicular Transport Proteins