Alpha-arrestins Aly1 and Aly2 regulate intracellular trafficking in response to nutrient signaling

Mol Biol Cell. 2010 Oct 15;21(20):3552-66. doi: 10.1091/mbc.E10-07-0636. Epub 2010 Aug 25.

Abstract

Extracellular signals regulate trafficking events to reorganize proteins at the plasma membrane (PM); however, few effectors of this regulation have been identified. β-Arrestins relay signaling cues to the trafficking machinery by controlling agonist-stimulated endocytosis of G-protein-coupled receptors. In contrast, we show that yeast α-arrestins, Aly1 and Aly2, control intracellular sorting of Gap1, the general amino acid permease, in response to nutrients. These studies are the first to demonstrate association of α-arrestins with clathrin and clathrin adaptor proteins (AP) and show that Aly1 and Aly2 interact directly with the γ-subunit of AP-1, Apl4. Aly2-dependent trafficking of Gap1 requires AP-1, which mediates endosome-to-Golgi transport, and the nutrient-regulated kinase, Npr1, which phosphorylates Aly2. During nitrogen starvation, Npr1 phosphorylation of Aly2 may stimulate Gap1 incorporation into AP-1/clathrin-coated vesicles to promote Gap1 trafficking from endosomes to the trans-Golgi network. Ultimately, increased Aly1-/Aly2-mediated recycling of Gap1 from endosomes results in higher Gap1 levels within cells and at the PM by diverting Gap away from trafficking pathways that lead to vacuolar degradation. This work defines a new role for arrestins in membrane trafficking and offers insight into how α-arrestins coordinate signaling events with protein trafficking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / deficiency*
  • Amino Acids / pharmacology
  • Arrestins / metabolism*
  • Cell Membrane / metabolism
  • Clathrin / metabolism
  • Endocytosis / drug effects
  • Endosomes / drug effects
  • Endosomes / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism*
  • Models, Biological
  • Mutation / genetics
  • Nitrogen / deficiency*
  • Nitrogen / pharmacology
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction / drug effects*
  • trans-Golgi Network / drug effects
  • trans-Golgi Network / metabolism

Substances

  • Amino Acids
  • Arrestins
  • Clathrin
  • Saccharomyces cerevisiae Proteins
  • Nitrogen