Cited by 520Cellular transport and secretionAutophagy in Disease and TherapyCalcium signaling and nucleotide metabolism

Oligomeric Complexes Link Rab5 Effectors with NSF and Drive Membrane Fusion via Interactions between EEA1 and Syntaxin 13

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McBride, Heidi M, Rybin, Vladimir, Murphy, Carol, Giner, Angelika, Teasdale, Rohan, Zerial, Marino·1999·Cell

Abstract

SNAREs and Rab GTPases cooperate in vesicle transport through a mechanism yet poorly understood. We now demonstrate that the Rab5 effectors EEA1 and Rabaptin-5/Rabex-5 exist on the membrane in high molecular weight oligomers, which also contain NSF. Oligomeric assembly is modulated by the ATPase activity of NSF. Syntaxin 13, the t-SNARE required for endosome fusion, is transiently incorporated into the large oligomers via direct interactions with EEA1. This interaction is required to drive fusion, since both dominant-negative EEA1 and synthetic peptides encoding the FYVE Zn2+ finger hinder the interaction and block fusion. We propose a novel mechanism whereby oligomeric EEA1 and NSF mediate the local activation of syntaxin 13 upon membrane tethering and, by analogy with viral fusion proteins, coordinate the assembly of a fusion pore.

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Crossref · 10.1016/s0092-8674(00)81966-2

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  • Rab5A is a marker of early phagosomes and facilitates downstream maturation by recruiting EEA1, which then binds NSF, Rabex5, and Rabaptin-5 and subsequently syntaxin13 to form a fusogenic complex with endosomes.

    “The small GTPase Rab5A is a marker of early phagosomes and facilitates downstream maturation by recruiting early endosomal antigen 1 (EEA1), which then binds NSF, Rabex5, and Rabaptin-5 and subsequently syntaxin13 to form a fusogenic complex with endosomes (22–24).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [22]

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Authors
McBride, H. M., Rybin, V., Murphy, C., Giner, A., Teasdale, R., & Zerial, M.
Affiliations
  • European Molecular Biology Laboratory (DE)
  • University of Ioannina (GR)
Corresponding author
Zerial, Marino
Venue
Cell
Publisher
Elsevier BV
Published
1999-08
Volume
98
Issue
3
Pages
377-386
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2126162952
Cited by
520
References
65
Citations by year
2026: 1 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 3 · 2021: 17 · 2020: 17 · 2019: 10 · 2018: 7 · 2017: 11 · 2016: 12 · 2015: 8 · 2014: 14 · 2013: 21 · 2012: 23
FWCI
18.39
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
EEA1, Rabaptin-5, NSF, t-SNARE, membrane fusion, endosome fusion, oligomeric complexes, snares, Rab GTPases, vesicle trafficking, ATPase activity
MeSH terms
Adenosine Triphosphatases, Amino Acid Sequence, Autoantigens, Carrier Proteins, HeLa Cells, Humans, Intracellular Membranes, Membrane Fusion, Membrane Proteins, Models, Biological, Molecular Sequence Data, Oligopeptides, Peptide Fragments, Endosomes, Biosensing Techniques, Zinc Fingers, GTP-Binding Proteins, GTP Phosphohydrolases, rab5 GTP-Binding Proteins, Vesicular Transport Proteins, SNARE Proteins, Qa-SNARE Proteins, N-Ethylmaleimide-Sensitive Proteins

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