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Cited by 3Cellular transport and secretionExtracellular vesicles in diseaseMicrotubule and mitosis dynamics

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Continuum architecture dynamics of vesicle tethering in exocytosis

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Puig-Tintó, Marta, Ortiz, Sebastian, Meek, Sasha, Coray, Raffaele, Betancur, Laura I., Hernández, Altair C., Castellet, Anna, Kramer, Eric, Hoess, Philipp, Mund, Markus, Molina-Ribagorda, Andrés, Izquierdo-Serra, Mercè, Oliva, Baldo, de Marco, Alex, Ries, Jonas, Castaño-Díez, Daniel, Manzo, Carlo, Gallego, Oriol·2026·Cell
DOI 10.1016/j.cell.2025.11.038

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Abstract

Essential for eukaryotes, multiple copies of the exocyst complex tether each secretory vesicle to the plasma membrane (PM) in constitutive exocytosis. The exocyst higher-order structure (ExHOS) that coordinates the action of these multiple exocysts remains unexplored. We integrated particle tracking, super-resolution microscopy, and cryo-electron tomography to time-resolve the continuum conformational landscape of the ExHOS and to functionally annotate its different conformations. We found that 7 exocysts form a flexible ring-shaped ExHOS that tethers vesicles at <45 nm from the PM. The ExHOS rapidly expands while pulling the vesicle toward the PM in a stepwise mechanism comprising three metastable states at 27, 18, and 5 nm from the PM. After fusion, Sec18 mediates the disassembly of the stationary ExHOS, a function that controls the rate of exocytosis. By resolving biophysical principles in situ, we reconstructed the spatiotemporal dynamics of the multimeric architecture controlling vesicle tethering in exocytosis.

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Metadata

Authors
Puig-Tintó, M., Ortiz, S., Meek, S., Coray, R., Betancur, L. I., Hernández, A. C., Castellet, A., Kramer, E., Hoess, P., Mund, M., Molina-Ribagorda, A., Izquierdo-Serra, M., Oliva, B., de Marco, A., Ries, J., Castaño-Díez, D., Manzo, C., & Gallego, O.
Affiliations
  • Universitat Pompeu Fabra (ES)
  • University of the Basque Country (ES)
  • European Molecular Biology Laboratory (DE)
  • Universitat de Barcelona (ES)
  • New York Structural Biology Center (US)
  • University of Vienna (AT)
  • Universitat de Vic - Universitat Central de Catalunya (ES)
Corresponding author
  • Ries, Jonas
  • Manzo, Carlo
  • Gallego, Oriol
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2026-02
Volume
189
Issue
4
Pages
1170-1184.e22
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2025.11.038
OpenAlex
W7124435907
Cited by
3
References
3
Citations by year
2026: 2
FWCI
6.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
Funders
  • State Agency of Research
  • Human Frontier Science Program
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
exocyst complex, vesicle tethering, exocytosis, Sec18, vesicle fusion, plasma membrane, metastable states, secretory vesicles, conformational dynamics, particle tracking, cryo-electron tomography
MeSH terms
Animals, Cell Membrane, Exocytosis, Membrane Fusion, Saccharomyces cerevisiae, Cryoelectron Microscopy, Secretory Vesicles, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, Electron Microscope Tomography

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