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

Elife. 2020 Aug 3:9: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.

Keywords: S. cerevisiae; alpha-arrestin; amino acid transporter; amino acids; cell biology; nutrient aquisition; starvation response; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism
  • Amino Acids / metabolism*
  • Arrestin / genetics
  • Arrestin / metabolism*
  • Endocytosis*
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Protein Transport
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / metabolism*
  • Ubiquitination

Substances

  • Amino Acid Transport Systems
  • Amino Acids
  • Arrestin
  • Endosomal Sorting Complexes Required for Transport
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligase Complexes
  • RSP5 protein, S cerevisiae