title: Eps1, a novel PDI-related protein involved in ER quality control in yeast.
abstract: PMA1 is an essential gene encoding the yeast plasma membrane [H(+)]ATPase. A pma1-D378N mutant has a dominant-negative effect on cell growth because both newly synthesized mutant and wild-type Pma1 molecules are retained and degraded in the endoplasmic reticulum (ER). Like other substrates for ER-associated degradation, Pma1-D378N is stabilized in mutants defective in components of the ubiquitination machinery. A genetic selection was performed for eps (ER-retained pma1 suppressing) mutants in which the growth defect caused by the D378N allele is suppressed. In an eps1 mutant, both mutant and wild-type Pma1 molecules are allowed to travel to the plasma membrane; however, normal retention of resident ER proteins Shr3 and Kar2 is not perturbed. Eps1 is a novel membrane protein belonging to the protein disulfide isomerase (PDI) family, and Eps1 co-localizes with Pma1-D378N in the ER. In the absence of Pma1-D378N, ER export of wild-type Pma1 is not affected by eps1 deletion, but export of the plasma membrane protein Gas1 is delayed. Because Eps1 is required for retention and degradation of Pma1-D378N, we propose a model in which Eps1 acts as a novel membrane-bound chaperone in ER quality control.
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Chang
mesh_terms: D000595:Amino Acid Sequence; D002268:Carboxypeptidases / Q000378:metabolism; D043402:Cathepsin A; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000235:genetics*; D006180:Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D013489:Suppression, Genetic; D014452:Ubiquitins / Q000378:metabolism
chemical_list: C402288:Eps1 protein, S cerevisiae; D005656:Fungal Proteins; C066709:GAS1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C434364:PMA2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D002268:Carboxypeptidases; D043402:Cathepsin A; C092477:PMA1 protein, S cerevisiae; D006180:Proton-Translocating ATPases; D019704:Protein Disulfide-Isomerases