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
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.
|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|
|Publisher:||Nature Publishing Group|