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Goliath family E3 ligases regulate the recycling endosome pathway via VAMP3 ubiquitylation
Author(s) -
Yamazaki Yasuo,
Schönherr Christina,
Varshney Gaurav K,
Dogru Murat,
Hallberg Bengt,
Palmer Ruth H
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.1
Subject(s) - biology , endosome , ubiquitin , microbiology and biotechnology , ubiquitin ligase , genetics , gene , intracellular
Diverse cellular processes depend on endocytosis, intracellular vesicle trafficking, sorting and exocytosis, processes regulated post‐transcriptionally by modifications such as phosphorylation and ubiquitylation. In addition to sorting to the lysosome, cargo is recycled to the plasma membrane via recycling endosomes. Here, we describe a role of the goliath gene family of protease‐associated (PA) domain E3 ligases in regulating recycling endosome trafficking. The two Drosophila members of this family—Goliath and Godzilla CG10277 —are located on endosomes, and both ectopic expression and loss‐of‐function lead to the accumulation of Rab5‐positive giant endosomes. Furthermore, the human homologue RNF167 exhibits similar behaviour. We show that the soluble N‐ethylmaleimide‐sensitive fusion attachment protein receptor (SNARE) protein VAMP3 is a target of these ubiquitin ligases, and that recycling endosome trafficking is abrogated in response to their activity. Furthermore, mutation of the Godzilla ubiquitylation target lysines on VAMP3 abrogates the formation of enlarged endosomes induced by either Godzilla or RNF167. Thus, Goliath ubiquitin ligases play a novel role in regulating recycling endosome trafficking via ubiquitylation of the VAMP3 SNARE protein.