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A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies

Nature Cell Biology volume 4, pages 117–123 (2002)Cite this article

Abstract

Membrane proteins with transmembrane domains (TMDs) that contain polar residues exposed to the lipid bilayer are selectively sorted into multivesicular bodies (MVBs) and delivered to the yeast vacuole. Sorting of some, although not all, proteins into these structures is mediated by ubiquitination. We have identified a transmembrane ubiquitin ligase, Tul1, that is resident in the Golgi apparatus and is required for the ubiquitination of proteins with polar TMDs, including vacuolar proteins such as carboxypeptidase S. We suggest that Tul1 provides quality control, identifying misfolded membrane proteins and marking them for transport to endosomes and degradation in the vacuole.

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Figure 1: A polar TMD residue induces ubiquitination of Pep12.
Figure 2: Requirements for entry into vacuoles.
Figure 3: TMD discrimination depends on Tul1.
Figure 4: Requirements for ubiquitination.
Figure 5: The Tul1 RING-domain binds Ubc4.
Figure 6: Localization of Tul1.
Figure 7: Sorting of proteins in the Golgi.

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Acknowledgements

We thank E. Hettema for the ubiquitin–GFP construct, and R. Haguenauer-Tsapis, M. Lewis, M. Black, S. Siniossoglou and K. Madura for advice and reagents. F. R was supported by the Swiss National Science foundation and by the European Molecular Biology Organization.

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  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    Fulvio Reggiori & Hugh R. B. Pelham

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Correspondence to Hugh R. B. Pelham.

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Reggiori, F., Pelham, H. A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies. Nat Cell Biol 4, 117–123 (2002). https://doi.org/10.1038/ncb743

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