1. Cell Biology
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Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids

  1. Vasyl Ivashov
  2. Johannes Zimmer
  3. Sinead Schwabl
  4. Jennifer Kahlhofer
  5. Sabine Weys
  6. Ronald Gstir
  7. Thomas Jackschitz
  8. Leopold Kremser
  9. Günther K Bonn
  10. Herbert Lindner
  11. Lukas A Huber
  12. Sebastien Leon
  13. Oliver Schmidt  Is a corresponding author
  14. David Teis
  1. Medical University of Innsbruck, Austria
  2. ADSI - Austrian Drug Screening Institute GmbH, Austria
  3. Université Paris-Diderot, France
Research Article
  • Cited 2
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Cite this article as: eLife 2020;9:e58246 doi: 10.7554/eLife.58246

Abstract

How cells adjust nutrient transport across their membranes is incompletely understood. Previously, we have shown that S. cerevisiae broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that the selective endocytosis of four AATs during starvation required the α-arrestin family protein Art2/Ecm21, an adaptor for the ubiquitin ligase Rsp5, and its induction through the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in AATs and thereby instructs Rsp5 to ubiquitinate proximal lysine residues. When amino acids are in excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis. Thus, amino acid excess or starvation activate complementary α-arrestin-Rsp5-complexes to control selective endocytosis and adapt nutrient acquisition.

Article and author information

Author details

  1. Vasyl Ivashov

    Institute for Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  2. Johannes Zimmer

    Institute for Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Sinead Schwabl

    Institute for Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Jennifer Kahlhofer

    Institute for Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Sabine Weys

    Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  6. Ronald Gstir

    ADSI - Austrian Drug Screening Institute GmbH, ADSI - Austrian Drug Screening Institute GmbH, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Thomas Jackschitz

    ADSI - Austrian Drug Screening Institute GmbH, ADSI - Austrian Drug Screening Institute GmbH, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  8. Leopold Kremser

    Division of Clinical Biochemistry, ProteinMicroAnalysis Facility, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  9. Günther K Bonn

    ADSI - Austrian Drug Screening Institute GmbH, ADSI - Austrian Drug Screening Institute GmbH, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  10. Herbert Lindner

    Division of Clinical Biochemistry, ProteinMicroAnalysis Facility, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  11. Lukas A Huber

    Institute for Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  12. Sebastien Leon

    Institut Jacques Monod, Université Paris-Diderot, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2536-8595
  13. Oliver Schmidt

    Institute for Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    For correspondence
    oliver.schmidt@i-med.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7921-4663
  14. David Teis

    Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8181-0253

Funding

European Molecular Biology Organization (ALTF 642-2012)

  • Oliver Schmidt

European Molecular Biology Organization (EMBOCOFUND2010)

  • Oliver Schmidt

European Molecular Biology Organization (GA-2010-267146)

  • Oliver Schmidt

Tiroler Wissenschaftsfond (2015)

  • Oliver Schmidt

Austrian Science Fund (FWF-Y444-B12)

  • David Teis

Austrian Science Fund (P30263)

  • David Teis

Austrian Science Fund (P29583)

  • David Teis

Agence Nationale de la Recherche (ANR-16-CE13-0002-01)

  • Sebastien Leon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Maya Schuldiner, Weizmann Institute, Israel

Publication history

  1. Received: April 24, 2020
  2. Accepted: August 1, 2020
  3. Accepted Manuscript published: August 3, 2020 (version 1)
  4. Accepted Manuscript updated: August 4, 2020 (version 2)
  5. Version of Record published: August 26, 2020 (version 3)

Copyright

© 2020, Ivashov et al.

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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