Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids
- Medical University of Innsbruck, Austria
- ADSI - Austrian Drug Screening Institute GmbH, Austria
- Université Paris-Diderot, France
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
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
- Maya Schuldiner, Weizmann Institute, Israel
Version history
- Received: April 24, 2020
- Accepted: August 1, 2020
- Accepted Manuscript published: August 3, 2020 (version 1)
- Accepted Manuscript updated: August 4, 2020 (version 2)
- 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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Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids
eLife 9:e58246.
https://doi.org/10.7554/eLife.58246
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