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PMID:15133481

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Citation

Pryor, PR, Mullock, BM, Bright, NA, Lindsay, MR, Gray, SR, Richardson, SC, Stewart, A, James, DE, Piper, RC and Luzio, JP (2004) Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events. EMBO Rep. 5:590-5

Abstract

Both heterotypic and homotypic fusion events are required to deliver endocytosed macromolecules to lysosomes and remodel late endocytic organelles. A trans-SNARE complex consisting of Q-SNAREs syntaxin 7, Vti1b and syntaxin 8 and the R-SNARE VAMP8 has been shown by others to be responsible for homotypic fusion of late endosomes. Using antibody inhibition experiments in rat liver cell-free systems, we confirmed this result, but found that the same Q-SNAREs can combine with an alternative R-SNARE, namely VAMP7, for heterotypic fusion between late endosomes and lysosomes. Co-immunoprecipitation demonstrated separate syntaxin 7 complexes with either VAMP7 or VAMP8 in solubilized rat liver membranes. Additionally, overexpression of the N-terminal domain of VAMP7, in cultured fibroblastic cells, inhibited the mixing of a preloaded lysosomal content marker with a marker delivered to late endosomes. These data show that combinatorial interactions of SNAREs determine whether late endosomes undergo homotypic or heterotypic fusion events.

Links

PubMed PMC1299070 Online version:10.1038/sj.embor.7400150

Keywords

Animals; Cell-Free System/immunology; Cell-Free System/metabolism; Endocytosis/physiology; Endosomes/immunology; Endosomes/metabolism; Immunoprecipitation; Lysosomes/immunology; Lysosomes/metabolism; Membrane Fusion; Membrane Proteins/immunology; Membrane Proteins/metabolism; PC12 Cells; Protein Transport/physiology; Qa-SNARE Proteins; R-SNARE Proteins; Rats; SNARE Proteins; Vesicular Transport Proteins/immunology; Vesicular Transport Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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