Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface

Cell. 2008 Nov 14;135(4):714-25. doi: 10.1016/j.cell.2008.09.025. Epub 2008 Oct 30.

Abstract

The diversity of plasma membrane (PM) proteins presents a challenge for the achievement of cargo-specific regulation of endocytosis. Here, we describe a family of proteins in yeast (ARTs, for arrestin-related trafficking adaptors) that function by targeting specific PM proteins to the endocytic system. Two members (Art1 and Art2) of the family were discovered in chemical-genetic screens, and they direct downregulation of distinct amino acid transporters triggered by specific stimuli. Sequence analysis revealed a total of nine ART family members in yeast. In addition to similarity to arrestins, the ARTs each contain multiple PY motifs. These motifs are required for recruitment of the Rsp5/Nedd4-like ubiquitin ligase, which modifies the cargoes as well as the ARTs. As a result, ubiquitinated cargoes are internalized and targeted to the vacuole (lysosome) for degradation. We propose that ARTs provide a cargo-specific quality-control pathway that mediates endocytic downregulation by coupling Rsp5/Nedd4 to diverse plasma membrane proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Arrestin / chemistry*
  • Carrier Proteins / metabolism
  • Cell Membrane / metabolism*
  • Endocytosis
  • Endosomal Sorting Complexes Required for Transport
  • Fungal Proteins / metabolism
  • Lysosomes / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Proteins / metabolism*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligase Complexes / metabolism

Substances

  • Arrestin
  • Carrier Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Fungal Proteins
  • LDB19 protein, S cerevisiae
  • Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Ubiquitin-Protein Ligase Complexes
  • RSP5 protein, S cerevisiae