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© The Rockefeller University Press, 0021-9525/2001//553 $5.00
The Journal of Cell Biology, Volume 152, Number 3, , 2001 553-562

Functional Differences in Yeast Protein Disulfide Isomerases

^a Department of Yeast Genetics, Carlsberg Laboratory, DK-2500 Copenhagen Valby, Denmark
Carlsberg Laboratory, Department of Yeast Genetics, Gamle Carlsberg Vej 10, DK-2500 Copenhagen Valby, Denmark.45 3327 476645 3327 5282

jrw{at}crc.dk

PDI1 is the essential gene encoding protein disulfide isomerase in yeast. The Saccharomyces cerevisiae genome, however, contains four other nonessential genes with homology to PDI1: MPD1, MPD2, EUG1, and EPS1. We have investigated the effects of simultaneous deletions of these genes. In several cases, we found that the ability of the PDI1 homologues to restore viability to a pdi1-deleted strain when overexpressed was dependent on the presence of low endogenous levels of one or more of the other homologues. This shows that the homologues are not functionally interchangeable. In fact, Mpd1p was the only homologue capable of carrying out all the essential functions of Pdi1p. Furthermore, the presence of endogenous homologues with a CXXC motif in the thioredoxin-like domain is required for suppression of a pdi1 deletion by EUG1 (which contains two CXXS active site motifs). This underlines the essentiality of protein disulfide isomerase-catalyzed oxidation. Most mutant combinations show defects in carboxypeptidase Y folding as well as in glycan modification. There are, however, no significant effects on ER-associated protein degradation in the various protein disulfide isomerase-deleted strains.

Key Words: protein disulfide isomerase • ER • protein folding • carboxypeptidase Y • Saccharomyces cerevisiae

© 2001 The Rockefeller University Press

Dr. Tachibana's present address is University of Washington, Department of Genetics, Seattle, WA 98195-7360.

Dr. Alsøe's present address is The Norwegian Radium Hospital, Department of Immunology, Montebello, 0310 Oslo, Norway.

Dr. Holst's present address is Danish Veterinary and Food Administration, Department of Food Safety and Toxicology, DK-2860 Søborg, Denmark.

Abbreviations used in this paper: 5-FOA, 5-fluoro-orotic acid; AMS, 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid; CPY, carboxypeptidase Y; ONPG, o-nitrophenyl-β-D-galactoside; PDI, protein disulfide isomerase.

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