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Bro1 coordinates deubiquitination in the ... by recruiting Doa4 to endosomes
Bro1 coordinates deubiquitination in the multivesicular body pathway by recruiting Doa4 to endosomes.
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Ubiquitination directs the sorting of cell surface receptors and other integral membrane proteins into the multivesicular body (MVB) pathway. Cargo proteins are subsequently deubiquitinated before their enclosure within MVB vesicles. In Saccharomyces cerevisiae, Bro1 functions at a late step of MVB sorting and is required for cargo protein deubiquitination. We show that the loss of Bro1 function is suppressed by the overexpression of DOA4, which encodes the ubiquitin thiolesterase required for the removal of ubiquitin from MVB cargoes. Overexpression of DOA4 restores cargo protein deubiquitination and sorting via the MVB pathway and reverses the abnormal endosomal morphology typical of bro1 mutant cells, resulting in the restoration of multivesicular endosomes. We further demonstrate that Doa4 interacts with Bro1 on endosomal membranes and that the recruitment of Doa4 to endosomes requires Bro1. Thus, our results point to a key role for Bro1 in coordinating the timing and location of deubiquitination by Doa4 in the MVB pathway.
Luhtala N, Odorizzi G
The Journal of cell biology
2004-08-30 00:00
166
5
717-29
Cells, Cultured,Cysteine Endopeptidases,Endocytosis,Endopeptidases,Endosomes,Intracellular Membranes,Microscopy, Electron,Multienzyme Complexes,Mutation,Proteasome Endopeptidase Complex,Protein Structure, Tertiary,Protein Transport,Receptors, Cell Surface,Saccharomyces cerevisiae,Saccharomyces cerevisiae Proteins,Transport Vesicles,Ubiquitin,Vesicular Transport Proteins,Bro1 protein, S cerevisiae,Multienzyme Complexes,Receptors, Cell Surface,Saccharomyces cerevisiae Proteins,Ubiquitin,Vesicular Transport Proteins,DOA4 protein, S cerevisiae,Endopeptidases,Cysteine Endopeptidases,Proteasome Endopeptidase Complex
Molecular, Cellular, and Developmental Biology, 347 UCB, University of Colorado, Boulder, CO 80309-0347, USA
J. Cell Biol.
NIGMS GM065505
0021-9525
10.1083/jcb.200403139
jcb.200403139
833
True
15326198
