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Peer-reviewedCC BYNature Cell Biology

In situ cryo-ET defines the ultrastructure of ER exit sites in human cells

  • Katie W Downes1,2
  • Julia R. Flood3
  • Andrea Nans4
  • Sander Egbert Van der Verren5,6,2
  • Anjon Audhya3
  • Giulia Zanetti7,8,9
9 affiliations
  1. 1Institute of Structural and Molecular Biology, University College London, London, UK
  2. 2The Francis Crick Institute, London, UK
  3. 3Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
  4. 4Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK
  5. 5Department of Plant Biotechnology and Bioinformatics, Ghent University - Center for Plant Systems Biology, Flemish Institute for Biotechnology, Ghent, Belgium
  6. 6Institute of Structural and Molecular Biology, Birkbeck College London, London, UK
  7. 7Institute of Structural and Molecular Biology, Birkbeck College London, London, UK. [email protected]
  8. 8Institute of Structural and Molecular Biology, University College London, London, UK. [email protected]
  9. 9The Francis Crick Institute, London, UK. [email protected]
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Abstract

Trafficking of secretory proteins from the endoplasmic reticulum (ER) to the Golgi apparatus comprises the first, essential steps towards the appropriate localization of 30% of eukaryotic proteins. Coat protein complexes COPII and COPI are involved in the forward and retrograde transport of cargo and cargo receptors between the ER and the Golgi, respectively. Although COPII forms coated vesicles in vitro, the biogenesis, morphology and organization of transport carriers in mammalian cells is subject to debate. Here we use in situ cryo-electron tomography and super-resolution fluorescence microscopy to reveal the molecular architecture of ER exit sites in human cells that were not perturbed with drugs, temperature blocks or overexpression systems. We visualize ribosome-exclusion zones enriched with COPII- and COPI-coated vesicles and thus resolve the debate regarding the existence of COPII-coated vesicles. COPII vesicles derive from ER membranes, whereas COPI vesicles originate from vesicular-tubular clusters that constitute the ER-Golgi intermediate compartment (ERGIC). We quantify coated vesicle morphology and positioning with respect to other ER exit site components, providing a molecular description of the organization of the mammalian early secretory pathway.

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Cite

BibTeXRIS
BibTeX
@article{downes2026situ,
  title = {{In situ cryo-ET defines the ultrastructure of ER exit sites in human cells}},
  author = {Katie W Downes and Julia R. Flood and Andrea Nans and Sander Egbert Van der Verren and Anjon Audhya and Giulia Zanetti},
  journal = {Nature Cell Biology},
  year = {2026},
  month = may,
  doi = {10.1038/s41556-026-01964-2},
  url = {https://doi.org/10.1038/s41556-026-01964-2},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - In situ cryo-ET defines the ultrastructure of ER exit sites in human cells
AU  - Katie W Downes
AU  - Julia R. Flood
AU  - Andrea Nans
AU  - Sander Egbert Van der Verren
AU  - Anjon Audhya
AU  - Giulia Zanetti
PY  - 2026
DA  - 2026/05/20
JO  - Nature Cell Biology
DO  - 10.1038/s41556-026-01964-2
UR  - https://doi.org/10.1038/s41556-026-01964-2
AB  - Trafficking of secretory proteins from the endoplasmic reticulum (ER) to the Golgi apparatus comprises the first, essential steps towards the appropriate localization of 30% of eukaryotic proteins. Coat protein complexes COPII and COPI are involved in the forward and retrograde transport of cargo and cargo receptors between the ER and the Golgi, respectively. Although COPII forms coated vesicles in vitro, the biogenesis, morphology and organization of transport carriers in mammalian cells is subject to debate. Here we use in situ cryo-electron tomography and super-resolution fluorescence microscopy to reveal the molecular architecture of ER exit sites in human cells that were not perturbed with drugs, temperature blocks or overexpression systems. We visualize ribosome-exclusion zones enriched with COPII- and COPI-coated vesicles and thus resolve the debate regarding the existence of COPII-coated vesicles. COPII vesicles derive from ER membranes, whereas COPI vesicles originate from vesicular-tubular clusters that constitute the ER-Golgi intermediate compartment (ERGIC). We quantify coated vesicle morphology and positioning with respect to other ER exit site components, providing a molecular description of the organization of the mammalian early secretory pathway.
SN  - 1465-7392
SN  - 1476-4679
ER  -