Continuum architecture dynamics of vesicle tethering in exocytosis

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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Publication Details

Journal
Cell
Published
2026-01-16
DOI
https://doi.org/10.1016/j.cell.2025.11.038
Citations
1
Primary Topic
Cellular transport and secretion
Type
article
Field-Weighted Citation Impact
23.07
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article

Continuum architecture dynamics of vesicle tethering in exocytosis

Eric M. Kramer, Mercè Izquierdo-Serra, Sebastian Ortiz, Laura Betancur et al.
1 citations
Cell
Cellular transport and secretion
23.07
article

Continuum architecture dynamics of vesicle tethering in exocytosis

Eric M. Kramer, Mercè Izquierdo-Serra, Sebastian Ortiz, Laura Betancur, Oriol Gallego, Carlo Manzo, Alex de Marco, Raffaele Coray, Markus Mund, Sasha Meek, Baldo Oliva, Daniel Castaño‐Díez, Anna Castellet, Jonas Ries, Andrés Molina-Ribagorda, Philipp Hoess, Marta Puig-Tintó, Altair C. Hernández
article en
1 citations

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.

CellVol. 189(4)
Universitat de Vic - Universitat Central de Catalunya (ES), University of the Basque Country (ES), Universitat Pompeu Fabra (ES), Max Perutz Labs (AT), New York Structural Biology Center (US), Instituto Biofisika (ES), Fundación Biofísica Bizkaia (ES), European Molecular Biology Laboratory (DE), Universitat de Barcelona (ES)
Openalex Percentile: Top 3%
Cellular transport and secretion
23.07
DOIOpen Access PDFOpenAlex
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