Export of a Cysteine-Free Misfolded Secretory Protein from the Endoplasmic Reticulum for Degradation Requires Interaction with Protein Disulfide Isomerase

Gillece, Pauline; Luz, Jose M.; Lennarz, William J.; Cruz, Francisco Javier de la; Römisch, Karin

doi:10.1083/jcb.147.7.1443

Cited by 179 publications

(151 citation statements)

References 65 publications

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“…This suggests that Pdi1 mediates reduction of disulphide in yeast in the absence of a mammalian ERdj5 ortholog. 45 In plants, PDI may perform the disulphide bond reduction role for ERAD substrates. Alternatively, plant ERdj3A, which has a TRX domain, may act as a reductase in a similar manner to ERdj5.…”

Section: Perspectivesmentioning

confidence: 99%

Emerging features of ER resident J-proteins in plants

Ohta¹,

Takaiwa²

2014

Plant Signaling & Behavior

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Section: Perspectivesmentioning

confidence: 99%

Emerging features of ER resident J-proteins in plants

Ohta¹,

Takaiwa²

2014

Plant Signaling & Behavior

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“…We have shown that deletion of 25 amino acids of the yeast PDI bЈ domain results in decreased glycosylation acceptor peptide binding (Pdi ⌬252-277; 40% peptide binding of wild type; ref. 25), and that deletion of the amino-terminal half of the bЈ domain and a small proportion of the preceding b domain reduces peptide binding to PDI to background levels (Pdi ⌬222-302; ref. 25).…”

Section: Release From Pdi Is Not Critical For Glycopeptide Export Fromentioning

confidence: 99%

The protein translocation channel mediates glycopeptide export across the endoplasmic reticulum membrane

Gillece

Pilon

Römisch

2000

Proc. Natl. Acad. Sci. U.S.A.

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Peptides and misfolded secretory proteins are transported efficiently from the endoplasmic reticulum (ER) lumen to the cytosol, where the proteins are degraded by proteasomes. Protein export depends on Sec61p, the ribosome-binding core component of the protein translocation channel in the ER membrane. We found that prebinding of ribosomes abolished export of a glycopeptide from yeast microsomes. Deletion of SSH1, which encodes a ribosomebinding Sec61p homologue in the ER, had no effect on glycopeptide export. A collection of cold-sensitive sec61 mutants displayed a variety of phenotypes: two mutants strongly defective in misfolded protein export from the ER, sec61-32 and sec61-41, displayed only minor peptide export defects. Glycopeptide export was severely impaired, however, in several sec61 mutants that were only marginally defective in misfolded protein export. In addition, a mutation in SEC63 strongly reduced peptide export from the ER. ER-luminal ATP was required for both misfolded protein and glycopeptide export. We conclude that the protein translocation channel in the ER membrane mediates glycopeptide transport across the ER membrane.

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“…Cells were radiolabeled and lysed, and proteins were immunoprecipitated or precipitated with concanavalin A (ConA)-Sepharose as in described by Gillece et al (1999). Lectin-precipitated samples were eluted with 1 M ␣-methyl mannoside in 20 mM Tris-HCl, pH7.5, 150 mM NaCl, 2 mM EDTA for 1 h at 30°C.…”

Section: Pulse-chase Experimentsmentioning

confidence: 99%

O-Mannosylation Protects Mutant Alpha-Factor Precursor from Endoplasmic Reticulum-associated Degradation

Harty

Strahl

Römisch

2001

MBoC

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Secretory proteins that fail to fold in the endoplasmic reticulum (ER) are transported back to the cytosol and degraded by proteasomes. It remains unclear how the cell distinguishes between folding intermediates and misfolded proteins. We asked whether misfolded secretory proteins are covalently modified in the ER before export. We found that a fraction of mutant alpha-factor precursor, but not the wild type, was progressively O-mannosylated in microsomes and in intact yeast cells by protein O-mannosyl transferase 2 (Pmt2p). O-Mannosylation increased significantly in vitro under ER export conditions, i.e., in the presence of ATP and cytosol, and this required export-proficient Sec61p in the ER membrane. Deletion of PMT2, however, did not abrogate mutant alpha-factor precursor degradation but, rather, enhanced its turnover in intact yeast cells. In vitro, O-mannosylated mutant alpha-factor precursor was stable and protease protected, and a fraction was associated with Sec61p in the ER lumen. Thus, prolonged ER residence allows modification of exposed O-mannosyl acceptor sites in misfolded proteins, which abrogates misfolded protein export from the ER at a posttargeting stage. We conclude that there is a limited window of time during which misfolded proteins can be removed from the ER before they acquire inappropriate modifications that can interfere with disposal through the Sec61 channel.

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Export of a Cysteine-Free Misfolded Secretory Protein from the Endoplasmic Reticulum for Degradation Requires Interaction with Protein Disulfide Isomerase

Cited by 179 publications

References 65 publications

Emerging features of ER resident J-proteins in plants

Emerging features of ER resident J-proteins in plants

The protein translocation channel mediates glycopeptide export across the endoplasmic reticulum membrane

O-Mannosylation Protects Mutant Alpha-Factor Precursor from Endoplasmic Reticulum-associated Degradation

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