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

• Published in: eLife 2020-08, Vol.9
• Main Authors: Ivashov, Vasyl, Zimmer, Johannes, Schwabl, Sinead, Kahlhofer, Jennifer, Weys, Sabine, Gstir, Ronald, Jakschitz, Thomas, Kremser, Leopold, Bonn, Günther K, Lindner, Herbert, Huber, Lukas A, Leon, Sebastien, Schmidt, Oliver, Teis, David
• Format: Article
• Language: English
• Subjects: alpha-arrestin; Amino Acid Transport Systems - genetics; Amino Acid Transport Systems - metabolism; amino acid transporter; Amino acids; Amino Acids - metabolism; Arrestin; Arrestin - genetics; Arrestin - metabolism; Cell Biology; Endocytosis; Endosomal Sorting Complexes Required for Transport - genetics; Endosomal Sorting Complexes Required for Transport - metabolism; Genomes; Homeostasis; Kinases; Lysine; Membranes; Metabolism; Microscopy; Nitrogen; nutrient aquisition; Nutrient transport; Phosphorylation; Plasma; Protein Transport; Proteins; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; starvation response; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligase Complexes - genetics; Ubiquitin-Protein Ligase Complexes - metabolism; Ubiquitination; Yeast
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.58246

How cells adjust nutrient transport across their membranes is incompletely understood. Previously, we have shown that 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.