Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface.
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.
Lin
Charles H
CH
Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
MacGurn
Jason A
JA
Chu
Tony
T
Stefan
Christopher J
CJ
Emr
Scott D
SD
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019393:Arrestin / Q000737:chemistry*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
D019393:Arrestin; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; C533888:LDB19 protein, S cerevisiae; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; C469287:RSP5 protein, S cerevisiae