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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
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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