'ER degradation' of a mutant yeast plasma membrane protein by the ubiquitin-proteasome pathway.
The yeast plasma membrane, uracil permease, undergoes ubiquitin-dependent endocytosis and subsequent degradation in the vacuole via a process that does not involve the proteasome. Cell-surface ubiquitination of this protein is mediated by the ubiquitin-protein ligase Npi1p/Rsp5p and involves Lys63-linked ubiquitin chains. This report describes the intracellular fate of a mutant form of uracil permease carrying a three amino acid insertion in a cytoplasmic loop. Most of this protein is not deployed beyond the ER, and is degraded by the 26S proteasome. Mutant permease degradation is almost unaffected in cells with impaired Npi1p/Rsp5p, but is dependent on the Ubc6p and Ubc7p ubiquitin-conjugating enzymes, suggesting that proteolysis of the protein requires its prior ubiquitination. Overproduction of a derivative of ubiquitin with a modified Lys48 strongly impairs mutant permease degradation. This suggests that, like other proteasome substrates, mutant permease might be polyubiquitinated with Lys48-linked ubiquitin chains. These findings provide an example of a yeast plasma membrane protein that is routed to the 'ER degradation' pathway, and highlight the versatility of the ubiquitin system.
Galan
J M
JM
Institut J. Monod, Université Paris VII-CNRS, France.
Cantegrit
B
B
Garnier
C
C
Namy
O
O
Haguenauer-Tsapis
R
R
D002462:Cell Membrane / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004721:Endoplasmic Reticulum; D005656:Fungal Proteins / Q000378:metabolism; D006056:Golgi Apparatus; D008025:Ligases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009154:Mutation; D033704:Nucleotide Transport Proteins; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
C035528:FUR4 protein, S cerevisiae; D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; D033704:Nucleotide Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases