1. Cell Biology
Download icon

Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and 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 39
  • Views 2,594
  • Annotations
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.

Metrics

  • 2,594
    Page views
  • 326
    Downloads
  • 39
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Developmental Biology
    Neta Erez et al.
    Research Article Updated

    A hallmark of aging is loss of differentiated cell identity. Aged Drosophila midgut differentiated enterocytes (ECs) lose their identity, impairing tissue homeostasis. To discover identity regulators, we performed an RNAi screen targeting ubiquitin-related genes in ECs. Seventeen genes were identified, including the deubiquitinase Non-stop (CG4166). Lineage tracing established that acute loss of Non-stop in young ECs phenocopies aged ECs at cellular and tissue levels. Proteomic analysis unveiled that Non-stop maintains identity as part of a Non-stop identity complex (NIC) containing E(y)2, Sgf11, Cp190, (Mod) mdg4, and Nup98. Non-stop ensured chromatin accessibility, maintaining the EC-gene signature, and protected NIC subunit stability. Upon aging, the levels of Non-stop and NIC subunits declined, distorting the unique organization of the EC nucleus. Maintaining youthful levels of Non-stop in wildtype aged ECs safeguards NIC subunits, nuclear organization, and suppressed aging phenotypes. Thus, Non-stop and NIC, supervise EC identity and protects from premature aging.

    1. Cell Biology
    2. Neuroscience
    Friederike Elisabeth Kohrs et al.
    Tools and Resources

    Rab GTPases are molecular switches that regulate membrane trafficking in all cells. Neurons have particular demands on membrane trafficking and express numerous Rab GTPases of unknown function. Here we report the generation and characterization of molecularly defined null mutants for all 26 rab genes in Drosophila. In flies, all rab genes are expressed in the nervous system where at least half exhibit particularly high levels compared to other tissues. Surprisingly, loss of any of these 13 nervous system-enriched Rabs yielded viable and fertile flies without obvious morphological defects. However, all 13 mutants differentially affected development when challenged with different temperatures, or neuronal function when challenged with continuous stimulation. We identified a synaptic maintenance defect following continuous stimulation for six mutants, including an autophagy-independent role of rab26. The complete mutant collection generated in this study provides a basis for further comprehensive studies of Rab GTPases during development and function in vivo.