Evidence map›Paper›PMID 27556945›Full record

ArticleNature2016

An endosomal tether undergoes an entropic collapse to bring vesicles together.

David H Murray, Marcus Jahnel, Janelle Lauer, Mario J Avellaneda, Nicolas Brouilly, Alice Cezanne, Hernán Morales-Navarrete, Enrico D Perini, Charles Ferguson, Andrei N Lupas and 4 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
11.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 179 citations in OpenAlex.

  1. Review
  2. Review
  3. The Rab5 effector Rabankyrin-5 mediates endosomal fusion and trafficking of human papillomavirus during early entry.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Motor Function of the Two-Component EEA1-Rab5 Revealed by dcFCCS.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  12. Article
  13. Review
  14. Rab21 recruits EEA1 and competes with Rab5 for Rabex-5 activation.Frontiers in cell and developmental biology · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. A model for collagen secretion by intercompartmental continuities.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. Article

19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

David H Murray *Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Marcus Jahnel *Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Janelle LauerMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Mario J AvellanedaMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Nicolas BrouillyMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Alice CezanneMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Hernán Morales-NavarreteMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Enrico D PeriniMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Charles FergusonInstitute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
Andrei N LupasDepartment of Protein Evolution, Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany.
Yannis KalaidzidisMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Robert G PartonInstitute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
Stephan W GrillMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Marino ZerialMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics · DEMax Planck Institute for the Physics of Complex Systems · DEThe University of Queensland · AUMax Planck Institute for Developmental Biology · DE

Funding

European Research Council 281903
6 · The paper itself

Abstract

An early step in intracellular transport is the selective recognition of a vesicle by its appropriate target membrane, a process regulated by Rab GTPases via the recruitment of tethering effectors. Membrane tethering confers higher selectivity and efficiency to membrane fusion than the pairing of SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) alone. Here we address the mechanism whereby a tethered vesicle comes closer towards its target membrane for fusion by reconstituting an endosomal asymmetric tethering machinery consisting of the dimeric coiled-coil protein EEA1 (refs 6, 7) recruited to phosphatidylinositol 3-phosphate membranes and binding vesicles harbouring Rab5. Surprisingly, structural analysis reveals that Rab5:GTP induces an allosteric conformational change in EEA1, from extended to flexible and collapsed. Through dynamic analysis by optical tweezers, we confirm that EEA1 captures a vesicle at a distance corresponding to its extended conformation, and directly measure its flexibility and the forces induced during the tethering reaction. Expression of engineered EEA1 variants defective in the conformational change induce prominent clusters of tethered vesicles in vivo. Our results suggest a new mechanism in which Rab5 induces a change in flexibility of EEA1, generating an entropic collapse force that pulls the captured vesicle towards the target membrane to initiate docking and fusion.

Indexed as

EntropyMembrane FusionAllosteric RegulationEndosomesGuanosine TriphosphateHumansOptical TweezersPhosphatidylinositol PhosphatesPliabilityProtein BindingProtein Conformationrab5 GTP-Binding ProteinsSNARE ProteinsVesicular Transport Proteinsearly endosome antigen 1Guanosine Triphosphatephosphatidylinositol 3-phosphatePhosphatidylinositol Phosphatesrab5 GTP-Binding ProteinsSNARE ProteinsVesicular Transport Proteins

Identifiers

PMID27556945
PMCPMC5142606
OpenAlexW2509259419

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.