Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis

Abstract

Ubiquitin functions as a signal for sorting cargo at multiple steps of the endocytic pathway and controls the activity of trans-acting components of the endocytic machinery (reviewed in refs 1, and 2). By contrast to proteasome degradation, which generally requires a polyubiquitin chain that is at least four subunits long3,4, internalization and sorting of endocytic cargo at the late endosome are mediated by mono-ubiquitination5,6,7,8. Here, we demonstrate that ubiquitin-interacting motifs (UIMs) found in epsins and Vps27p (ref. 9) from Saccharomyces cerevisiae are required for ubiquitin binding and protein transport. Epsin UIMs are important for the internalization of receptors into vesicles at the plasma membrane. Vps27p UIMs are necessary to sort biosynthetic and endocytic cargo into vesicles that bud into the lumen of a late endosomal compartment, the multivesicular body. We propose that mono-ubiquitin regulates internalization and endosomal sorting by interacting with modular ubiquitin-binding domains in core components of the protein transport machinery. UIM domains are found in a broad spectrum of proteins, consistent with the idea that mono-ubiquitin can function as a regulatory signal to control diverse biological activities.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Epsins, Vps27p and Ede1p are mono-ubiquitin-binding proteins.
Figure 2: UIM domains directly interact with ubiquitin through ubiquitin Ile 44.
Figure 3: Ent1p UIM domains and Ede1p function redundantly to promote ubiquitinated receptor internalization.
Figure 4: Vps27p UIMs are required for sorting of biosynthetic and endocytic ubiquitinated cargo into MVB vesicles.

Similar content being viewed by others

References

  1. Hicke, L. Cell 106, 527–530 (2001).

    Article  CAS  Google Scholar 

  2. Dupre, S., Volland, C. & Haguenauer-Tsapis, R. Curr. Biol. 11, R932–934 (2001).

    Article  CAS  Google Scholar 

  3. Chau, V. et al. Science 243, 1576–1583 (1989).

    Article  CAS  Google Scholar 

  4. Thrower, J. S., Hoffman, L., Rechsteiner, M. & Pickart, C. M. EMBO J. 19, 94–102 (2000).

    Article  CAS  Google Scholar 

  5. Terrell, J., Shih, S., Dunn, R. & Hicke, L. Mol. Cell 1, 193–202 (1998).

    Article  CAS  Google Scholar 

  6. Katzmann, D. J., Babst, M. & Emr, S. D. Cell 106, 145–155 (2001).

    Article  CAS  Google Scholar 

  7. Reggiori, F. & Pelham, H. R. EMBO J. 20, 5176–5186 (2001).

    Article  CAS  Google Scholar 

  8. Urbanowski, J. & Piper, R. C. Traffic 2, 623–631 (2001).

    Article  Google Scholar 

  9. Hofmann, K. & Falquet, L. Trends Biochem. Sci. 26, 347–350 (2001).

    Article  CAS  Google Scholar 

  10. Hofmann, K. & Bucher, P. Trends Biochem. Sci. 21, 172–173 (1996).

    Article  CAS  Google Scholar 

  11. Bertolaet, B. L. et al. Nature Struct. Biol. 8, 417–422 (2001).

    Article  CAS  Google Scholar 

  12. Chen, L., Shinde, U., Ortolan, T. G. & Madura, K. EMBO Rep. 2, 933–938 (2001).

    Article  CAS  Google Scholar 

  13. Wilkinson, C. R. et al. Nature Cell Biol. 3, 939–943 (2001).

    Article  CAS  Google Scholar 

  14. Young, P., Deveraux, Q., Beal, R. E., Pickart, C. M. & Rechsteiner, M. J. Biol. Chem. 273, 5461–5467 (1998).

    Article  CAS  Google Scholar 

  15. Wendland, B., Steece, K. E. & Emr, S. D. EMBO J. 18, 4383–4393 (1999).

    Article  CAS  Google Scholar 

  16. Piper, R. C., Cooper, A. A., Yang, H. & Stevens, T. H. J. Cell Biol. 131, 603–617 (1995).

    Article  CAS  Google Scholar 

  17. Gagny, B. et al. J. Cell Sci. 113, 3309–3319 (2000).

    CAS  PubMed  Google Scholar 

  18. Chen, H. et al. Nature 394, 793–797 (1998).

    Article  CAS  Google Scholar 

  19. Komada, M., Masaki, R., Yamamoto, A. & Kitamura, N. J. Biol. Chem. 272, 20538–20544 (1997).

    Article  CAS  Google Scholar 

  20. Chin, L. S., Raynor, M. C., Wei, X., Chen, H. Q. & Li, L. J. Biol. Chem. 276, 7069–7078 (2001).

    Article  CAS  Google Scholar 

  21. Benmerah, A. et al. J. Cell Biol. 140, 1055–1062 (1998).

    Article  CAS  Google Scholar 

  22. Beal, R., Deveraux, Q., Xia, G., Rechsteiner, M. & Pickart, C. Proc. Natl Acad. Sci. USA 93, 861–866 (1996).

    Article  CAS  Google Scholar 

  23. Shih, S. C., Sloper-Mould, K. E. & Hicke, L. EMBO J. 19, 187–198 (2000).

    Article  CAS  Google Scholar 

  24. Nakatsu, F. et al. J. Biol. Chem. 275, 26213–26219 (2000).

    Article  CAS  Google Scholar 

  25. Sloper-Mould, K. E., Pickart, C. M. & Hicke, L. J. Biol. Chem. 276, 30483–30489 (2001).

    Article  CAS  Google Scholar 

  26. Rosenthal, J. A. et al. J. Biol. Chem. 274, 33959–33965 (1999).

    Article  CAS  Google Scholar 

  27. Hicke, L. & Riezman, H. Cell 84, 277–287 (1996).

    Article  CAS  Google Scholar 

  28. Odorizzi, G., Babst, M. & Emr, S. D. Cell 95, 847–858 (1998).

    Article  CAS  Google Scholar 

  29. Koegl, M. et al. Cell 96, 635–644 (1999).

    Article  CAS  Google Scholar 

  30. Dulic, V. et al. Methods Enzymol. 194, 697–710 (1991).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to S. Francis for constructing 6×His–UIM expression plasmids, R. Dunn for construction of HA-tagged ENT plasmids and critical comments on the manuscript, R. Lamb for 12CA5 HA antiserum and L. Robinson for pHA–YCK2. This work was supported by a National Institutes of Health training grant to S.S. (T32GM08061), an American Cancer Society Postdoctoral Fellowship to D.K., the Howard Hughes Medical Institute for S.E., the Searle Scholars program for L.H., and the NIH to L.H. (DK53257) and S.E. (CA58689).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Scott D. Emr or Linda Hicke.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Table S1

Yeast strains. (PDF 23 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shih, S., Katzmann, D., Schnell, J. et al. Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis. Nat Cell Biol 4, 389–393 (2002). https://doi.org/10.1038/ncb790

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb790

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing