Abstract
Membrane proteins that are degraded in the vacuole of Saccharomyces cerevisiae are sorted into discrete intralumenal vesicles, analogous to the internal membranes of multi-vesiculated bodies (MVBs). Recently, it has shown that the attachment of ubiquitin (Ub) mediates sorting into lumenal membranes1. We describe a complex of Vps27p and Hse1p that localizes to endosomal compartments and is required for the recycling of Golgi proteins, formation of lumenal membranes and sorting of ubiquitinated proteins into those membranes. The Vps27p–Hse1p complex binds to Ub and requires multiple Ub Interaction Motifs (UIMs). Mutation of these motifs results in specific defects in the sorting of ubiquitinated proteins into the vacuolar lumen. However, the recycling of Golgi proteins and the generation of lumenal membranes proceeds normally in Δ UIM mutants. These data support a model in which the Vps27p–Hse1p complex has multiple functions at the endosome, one of which is as a sorting receptor for ubiquitinated membrane proteins destined for degradation.
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Acknowledgements
We thank S. Moye-Rowley, B. Cohen, T. Stevens and L. Weisman for helpful suggestions. We also thank the University of Iowa Central Microscopy Facility for technical assistance with electron microscopy. This work was supported by National Institutes of Health grant RO1 GM58202.
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Figure 1. Hse1-GFP function and Immunolocalization of Vps27 in hse1 mutant cells. a, The (PDF 333 kb)
Figure 2. The Ub-independent sorting of Sna3-GFP is normal in ΔUIM cells.
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Bilodeau, P., Urbanowski, J., Winistorfer, S. et al. The Vps27p–Hse1p complex binds ubiquitin and mediates endosomal protein sorting. Nat Cell Biol 4, 534–539 (2002). https://doi.org/10.1038/ncb815
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DOI: https://doi.org/10.1038/ncb815
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