A genome-wide screen identifies Yos9p as essential for ER-associated degradation of glycoproteins.
We undertook a growth-based screen exploiting the degradation of CTL*, a chimeric membrane-bound ERAD substrate derived from soluble lumenal CPY*. We screened the Saccharomyces cerevisiae genomic deletion library containing approximately 5000 viable strains for mutants defective in endoplasmic reticulum (ER) protein quality control and degradation (ERAD). Among the new gene products we identified Yos9p, an ER-localized protein previously involved in the processing of GPI anchored proteins. We show that deficiency in Yos9p affects the degradation only of glycosylated ERAD substrates. Degradation of non-glycosylated substrates is not affected in cells lacking Yos9p. We propose that Yos9p is a lectin or lectin-like protein involved in the quality control of N-glycosylated proteins. It may act sequentially or in concert with the ERAD lectin Htm1p/Mnl1p (EDEM) to prevent secretion of malfolded glycosylated proteins and deliver them to the cytosolic ubiquitin-proteasome machinery for elimination.
Buschhorn
Bettina A
BA
Institut für Biochemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
Kostova
Zlatka
Z
Medicherla
Balasubrahmanyam
B
Wolf
Dieter H
DH
D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011786:Quality Control; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013462:Sulfur Radioisotopes; D013696:Temperature
D002352:Carrier Proteins; D006023:Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D013462:Sulfur Radioisotopes; C495027:Yos9 protein, S cerevisiae; D008715:Methionine