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Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events

Pryor, P.R., Mullock, B.M., Bright, N.A., Lindsay, M.R., Gray, S.R., Richardson, S.C.W., Stewart, A., James, D.E., Piper, R.C. and Luzio, J.P. (2004) Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events. EMBO Reports, 5 (5). pp. 590-595. ISSN 1469-221X

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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.

Item Type: Article
Institution: The University of York
Academic Units: The University of York > Biology (York)
Depositing User: York RAE Import
Date Deposited: 19 Jun 2009 11:21
Last Modified: 19 Jun 2009 11:21
Published Version: http://dx.doi.org/10.1038/sj.embor.7400150
Status: Published
Publisher: Nature Publishing Group
Identification Number: 10.1038/sj.embor.7400150
URI: http://eprints.whiterose.ac.uk/id/eprint/6040

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