Goliath family E3 ligases regulate the recycling endosome pathway via VAMP3 ubiquitylation

EMBO J. 2013 Feb 20;32(4):524-37. doi: 10.1038/emboj.2013.1. Epub 2013 Jan 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Endosomes / genetics
  • Endosomes / metabolism*
  • HEK293 Cells
  • Humans
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination / physiology*
  • Vesicle-Associated Membrane Protein 3 / genetics
  • Vesicle-Associated Membrane Protein 3 / metabolism*


  • DNA-Binding Proteins
  • Drosophila Proteins
  • VAMP3 protein, human
  • Vesicle-Associated Membrane Protein 3
  • gol protein, Drosophila
  • TTC3 protein, human
  • Ubiquitin-Protein Ligases