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.