Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13.

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.
Mesh Terms:
Adenosine Triphosphatases, Amino Acid Sequence, Autoantigens, Biosensing Techniques, Carrier Proteins, Endosomes, GTP Phosphohydrolases, GTP-Binding Proteins, Hela Cells, Humans, Intracellular Membranes, Membrane Fusion, Membrane Proteins, Models, Biological, Molecular Sequence Data, N-Ethylmaleimide-Sensitive Proteins, Oligopeptides, Peptide Fragments, Qa-SNARE Proteins, SNARE Proteins, Vesicular Transport Proteins, Zinc Fingers, rab5 GTP-Binding Proteins
Cell
Date: Aug. 06, 1999
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