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Peer-reviewedCC BY 4.0Molecular Biology of the Cell

Sequential restriction of SNARE-mediated fusion by the COPII inner coat and SNARE chaperones

  • E. J. Mackey1
  • T. Takenaka1
  • E. A. Miller2,3
  • A. J. Merz1,4,5
5 affiliations
  1. 1Department of Biochemistry, Seattle, WA 98125
  2. 2MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
  3. 3Division of Cell and Developmental Biology, University of Dundee, School of Life Sciences, Dundee DD1 4HN Scotland, UK
  4. 4Department of Neuroscience & Biophysics, Seattle, WA 98125
  5. 5Department of Microbiology, University of Washington, Seattle, WA 98125
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Abstract

SNARE-mediated fusion requires assembly of four SNARE domains (Qa, Qb, Qc, R) distributed across two membranes, with an SM (Sec1/Munc-18 family) chaperone catalyzing this assembly. We investigated topological requirements for the four SNAREs (Sed5, Bos1, Bet1, Sec22) that mediate ER-Golgi fusion using in vitro assays. In the presence of the cognate SM Sly1, we find that the R SNARE must be in trans to the Qa and Qb SNAREs. The Qc SNARE functions on either membrane but is most active in cis to Qa and Qb. These results prompted us to look upstream, at COPII-SNARE interactions. The assembled COPII coat is known to block fusion. We discovered that of five COPII core subunits, the Sar1 GTPase and Sec23/Sec24 subunits were necessary and sufficient to prevent fusion for prolonged periods, and that Sar1 was dispensable for inhibition over short periods. When Sec24 interactions with R and Qc SNAREs were disrupted, inhibition was relieved, indicating that SNARE sequestration by COPII on the nascent carrier prevents fusion. These observations help to explain how appropriate fusion events are facilitated while inappropriate events are deterred.

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Cite

BibTeXRIS
BibTeX
@article{mackey2026sequential,
  title = {{Sequential restriction of SNARE-mediated fusion by the COPII inner coat and SNARE chaperones}},
  author = {E. J. Mackey and T. Takenaka and E. A. Miller and A. J. Merz},
  journal = {Molecular Biology of the Cell},
  year = {2026},
  month = oct,
  doi = {10.1091/mbc.e26-08-0357-t},
  url = {https://doi.org/10.1091/mbc.e26-08-0357-t},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Sequential restriction of SNARE-mediated fusion by the COPII inner coat and SNARE chaperones
AU  - E. J. Mackey
AU  - T. Takenaka
AU  - E. A. Miller
AU  - A. J. Merz
PY  - 2026
DA  - 2026/10/26
JO  - Molecular Biology of the Cell
DO  - 10.1091/mbc.e26-08-0357-t
UR  - https://doi.org/10.1091/mbc.e26-08-0357-t
AB  - SNARE-mediated fusion requires assembly of four SNARE domains (Qa, Qb, Qc, R) distributed across two membranes, with an SM (Sec1/Munc-18 family) chaperone catalyzing this assembly. We investigated topological requirements for the four SNAREs (Sed5, Bos1, Bet1, Sec22) that mediate ER-Golgi fusion using in vitro assays. In the presence of the cognate SM Sly1, we find that the R SNARE must be in trans to the Qa and Qb SNAREs. The Qc SNARE functions on either membrane but is most active in cis to Qa and Qb. These results prompted us to look upstream, at COPII-SNARE interactions. The assembled COPII coat is known to block fusion. We discovered that of five COPII core subunits, the Sar1 GTPase and Sec23/Sec24 subunits were necessary and sufficient to prevent fusion for prolonged periods, and that Sar1 was dispensable for inhibition over short periods. When Sec24 interactions with R and Qc SNAREs were disrupted, inhibition was relieved, indicating that SNARE sequestration by COPII on the nascent carrier prevents fusion. These observations help to explain how appropriate fusion events are facilitated while inappropriate events are deterred.
SN  - 1059-1524
SN  - 1939-4586
ER  -