The yeast multidrug transporter Pdr5 of the plasma membrane is ubiquitinated prior to endocytosis and degradation in the vacuole.
We have recently demonstrated that the Pdr5 ATP binding cassette multidrug transporter is a short-lived protein, whose biogenesis involves cell surface targeting followed by endocytosis and delivery to the vacuole for proteolytic turnover [Egner, R., Mahé, Y., Pandjaitan, R., and Kuchler, K. (1995) Mol. Cell. Biol. 15, 5879-5887]. Using c-myc epitope-tagged ubiquitin, we now have shown that Pdr5 is a ubiquitinated plasma membrane protein in vivo. Ubiquitination of Pdr5 was detected in both wild type and conditional end mutants defective in endocytic vesicle formation. Likewise, the Ste6 a-factor pheromone transporter, which represents another short-lived ABC transporter whose turnover requires vacuolar proteolysis, was also found to be ubiquitinated, and ubiquitin-modified Ste6 massively accumulated in end4 mutants at the restrictive temperature. By contrast, the plasma membrane ATPase Pma1, a long-lived and metabolically very stable protein, was found not to be ubiquitinated. Our results imply a novel function for ubiquitin in protein trafficking and suggest that ubiquitination of certain short-lived plasma membrane proteins may trigger their endocytic delivery to the vacuole for proteolytic turnover.
Egner
R
R
Department of Molecular Genetics, University and Biocenter Vienna, Austria.
Kuchler
K
K
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry; D004705:Endocytosis; D005656:Fungal Proteins / Q000378:metabolism*; D006388:Hemagglutinins; D008565:Membrane Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D005656:Fungal Proteins; D006388:Hemagglutinins; D008565:Membrane Proteins; C092438:PDR5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins