Export of a cysteine-free misfolded secretory protein from the endoplasmicreticulum for degradation requires interaction with protein disulfide isomerase

Citation
P. Gillece et al., Export of a cysteine-free misfolded secretory protein from the endoplasmicreticulum for degradation requires interaction with protein disulfide isomerase, J CELL BIOL, 147(7), 1999, pp. 1443-1456
Citations number
61
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
147
Issue
7
Year of publication
1999
Pages
1443 - 1456
Database
ISI
SICI code
0021-9525(199912)147:7<1443:EOACMS>2.0.ZU;2-3
Abstract
Protein disulfide isomerase (PDI) interacts with secretory proteins, irresp ective of their thiol content, late during translocation into the ER; thus, PDI may be part of the quality control machinery in the ER. We used yeast pdi1 mutants with deletions in the putative peptide binding region of the m olecule to investigate its role in the recognition of misfolded secretory p roteins in the ER and their export to the cytosol for degradation. Our pdi1 deletion mutants are deficient in the export of a misfolded cysteine-free secretory protein across the ER membrane to the cytosol for degradation, bu t ER-to-Golgi complex transport of properly folded secretory proteins is on ly marginally affected. We demonstrate by chemical cross-linking that PDI s pecifically interacts with the misfolded secretory protein and that mutant forms of PDI have a lower affinity for this protein. In the ER of the pdi1 mutants, a higher proportion of the misfolded secretory protein remains ass ociated with BiP, and in export-deficient sec61 mutants, the misfolded secr etory protein remain bounds to PDI. We conclude that the chaperone PDI is p art of the quality control machinery in the ER that recognizes terminally m isfolded secretory proteins and targets them to the export channel in the E R membrane.