Article

Permease recycling and ubiquitination status reveal a particular role for Bro1 in the multivesicular body pathway.

Laboratoire de Physiologie Cellulaire, Université Libre de Bruxelles, B-6041 Gosselies, Belgium.
Journal of Biological Chemistry (impact factor: 4.77). 01/2004; 278(50):50732-43. DOI:10.1074/jbc.M306953200
Source: PubMed

ABSTRACT Ubiquitination of the yeast Gap1 permease at the plasma membrane triggers its endocytosis followed by targeting to the vacuolar lumen for degradation. We previously identified Bro1 as a protein essential to this down-regulation. In this study, we show that Bro1 is essential neither to ubiquitination nor to the early steps of Gap1 endocytosis. Bro1 rather intervenes at a late step of the multivesicular body (MVB) pathway, after the core components of the endosome-associated ESCRT-III protein complex and before or in conjunction with Doa4, the ubiquitin hydrolase mediating protein deubiquitination prior to their incorporation into MVB vesicles. Bro1 markedly differs from other class E vacuolar protein sorting factors involved in MVB sorting as lack of Bro1 leads to recycling of the internalized permease back to the plasma membrane by passing through the Golgi. This recycling seems to be accompanied by deubiquitination of the permease and unexpectedly requires a normal endosome-to-vacuole transport function.

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Keywords

Bro1
 
class E vacuolar protein sorting factors
 
core components
 
deubiquitination
 
Doa4
 
endosome-associated ESCRT-III protein complex
 
internalized permease
 
multivesicular body
 
MVB
 
MVB sorting
 
MVB vesicles
 
normal endosome-to-vacuole transport function
 
permease
 
plasma membrane
 
plasma membrane triggers
 
recycling
 
ubiquitin hydrolase mediating protein deubiquitination
 
Ubiquitination
 
yeast Gap1 permease