1. Cell Biology
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Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and the ubiquitin ligase Rsp5

  1. Michel Becuwe
  2. Sébastien Léon  Is a corresponding author
  1. Harvard School of Public Health, United States
  2. Institut Jacques Monod, Université Paris-Diderot, CNRS, France
Research Article
  • Cited 38
  • Views 2,588
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Cite this article as: eLife 2014;3:e03307 doi: 10.7554/eLife.03307

Abstract

After endocytosis, membrane proteins can recycle to the cell membrane or be degraded in lysosomes. Cargo ubiquitylation favors their lysosomal targeting and can be regulated by external signals, but the mechanism is ill-defined. Here, we studied the post-endocytic trafficking of Jen1, a yeast monocarboxylate transporter, using microfluidics-assisted live-cell imaging. We show that the ubiquitin ligase Rsp5 and the glucose-regulated arrestin-related (ART) protein Rod1, involved in the glucose-induced internalization of Jen1, are also required for the post-endocytic sorting of Jen1 to the yeast lysosome. This new step takes place at the trans-Golgi network (TGN), where Rod1 localizes dynamically upon triggering endocytosis. Indeed, transporter trafficking to the TGN after internalization is required for their degradation. Glucose removal promotes Rod1 relocalization to the cytosol and Jen1 deubiquitylation, allowing transporter recycling when the signal is only transient. Therefore, nutrient availability regulates transporter fate through the localization of the ART/Rsp5 ubiquitylation complex at the TGN.

Article and author information

Author details

  1. Michel Becuwe

    Harvard School of Public Health, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sébastien Léon

    Institut Jacques Monod, Université Paris-Diderot, CNRS, Paris, France
    For correspondence
    leon.sebastien@ijm.univ-paris-diderot.fr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Ivan Dikic, Goethe University Medical School, Germany

Publication history

  1. Received: May 7, 2014
  2. Accepted: November 4, 2014
  3. Accepted Manuscript published: November 7, 2014 (version 1)
  4. Accepted Manuscript updated: November 13, 2014 (version 2)
  5. Version of Record published: November 26, 2014 (version 3)

Copyright

© 2014, Becuwe & Léon

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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