Dynamic retention of Ero1α and Ero1β in the endoplasmic reticulum by interactions with PDI and ERp44

Mieko Otsu, Gloria Bertoli, Claudio Fagioli, Elena Guerini-Rocco, Silvia Nerini-Molteni, Elena Ruffato, Roberto Sitia

Research output: Contribution to journalArticle

Abstract

Disulfide bonds are formed in the endoplasmic reticulum (ER) by sequential interchange reactions: Ero1α and Ero1β transfer oxidative equivalents to protein disulfide isomerase (PDI), which in turn oxidizes cargo proteins. Neither Ero1α nor Ero1β contains known ER localization motif (s), raising the question of how they are retained in this organelle. Here the authors show that, unlike endogenous molecules, overexpressed Ero1α and Ero1β are secreted by HeLa transfectants, suggesting saturation of their normal retention mechanism(s). Co-expression of either PDI or ERp44 prevents Ero1 secretion in a KDEL/RDEL dependent way. Covalent interactions between ERp44 and Ero1 are essential for retention. In contrast, a mutant PDI lacking the four cysteines in the two active sites still inhibits secretion, albeit less efficiently. PDI and ERp44 compete for Ero1 binding. PDI also prevents Ero1 aggregation and dimerization, thus chaperoning its own oxidase. This dynamic retention mechanism of Ero1 may be important for fine-tuning the regulation of ER redox homeostasis and quality control.

Original languageEnglish
Pages (from-to)274-282
Number of pages9
JournalAntioxidants and Redox Signaling
Volume8
Issue number3-4
DOIs
Publication statusPublished - Mar 2006

Fingerprint

Protein Disulfide-Isomerases
Endoplasmic Reticulum
Dimerization
Interchanges
Mutant Proteins
Disulfides
Quality Control
Organelles
Oxidation-Reduction
Quality control
Cysteine
Catalytic Domain
Oxidoreductases
Homeostasis
Agglomeration
Tuning
Molecules
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Dynamic retention of Ero1α and Ero1β in the endoplasmic reticulum by interactions with PDI and ERp44. / Otsu, Mieko; Bertoli, Gloria; Fagioli, Claudio; Guerini-Rocco, Elena; Nerini-Molteni, Silvia; Ruffato, Elena; Sitia, Roberto.

In: Antioxidants and Redox Signaling, Vol. 8, No. 3-4, 03.2006, p. 274-282.

Research output: Contribution to journalArticle

Otsu, Mieko ; Bertoli, Gloria ; Fagioli, Claudio ; Guerini-Rocco, Elena ; Nerini-Molteni, Silvia ; Ruffato, Elena ; Sitia, Roberto. / Dynamic retention of Ero1α and Ero1β in the endoplasmic reticulum by interactions with PDI and ERp44. In: Antioxidants and Redox Signaling. 2006 ; Vol. 8, No. 3-4. pp. 274-282.
@article{0d29b9348b904e74b5d4b572aa235790,
title = "Dynamic retention of Ero1α and Ero1β in the endoplasmic reticulum by interactions with PDI and ERp44",
abstract = "Disulfide bonds are formed in the endoplasmic reticulum (ER) by sequential interchange reactions: Ero1α and Ero1β transfer oxidative equivalents to protein disulfide isomerase (PDI), which in turn oxidizes cargo proteins. Neither Ero1α nor Ero1β contains known ER localization motif (s), raising the question of how they are retained in this organelle. Here the authors show that, unlike endogenous molecules, overexpressed Ero1α and Ero1β are secreted by HeLa transfectants, suggesting saturation of their normal retention mechanism(s). Co-expression of either PDI or ERp44 prevents Ero1 secretion in a KDEL/RDEL dependent way. Covalent interactions between ERp44 and Ero1 are essential for retention. In contrast, a mutant PDI lacking the four cysteines in the two active sites still inhibits secretion, albeit less efficiently. PDI and ERp44 compete for Ero1 binding. PDI also prevents Ero1 aggregation and dimerization, thus chaperoning its own oxidase. This dynamic retention mechanism of Ero1 may be important for fine-tuning the regulation of ER redox homeostasis and quality control.",
author = "Mieko Otsu and Gloria Bertoli and Claudio Fagioli and Elena Guerini-Rocco and Silvia Nerini-Molteni and Elena Ruffato and Roberto Sitia",
year = "2006",
month = "3",
doi = "10.1089/ars.2006.8.274",
language = "English",
volume = "8",
pages = "274--282",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "3-4",

}

TY - JOUR

T1 - Dynamic retention of Ero1α and Ero1β in the endoplasmic reticulum by interactions with PDI and ERp44

AU - Otsu, Mieko

AU - Bertoli, Gloria

AU - Fagioli, Claudio

AU - Guerini-Rocco, Elena

AU - Nerini-Molteni, Silvia

AU - Ruffato, Elena

AU - Sitia, Roberto

PY - 2006/3

Y1 - 2006/3

N2 - Disulfide bonds are formed in the endoplasmic reticulum (ER) by sequential interchange reactions: Ero1α and Ero1β transfer oxidative equivalents to protein disulfide isomerase (PDI), which in turn oxidizes cargo proteins. Neither Ero1α nor Ero1β contains known ER localization motif (s), raising the question of how they are retained in this organelle. Here the authors show that, unlike endogenous molecules, overexpressed Ero1α and Ero1β are secreted by HeLa transfectants, suggesting saturation of their normal retention mechanism(s). Co-expression of either PDI or ERp44 prevents Ero1 secretion in a KDEL/RDEL dependent way. Covalent interactions between ERp44 and Ero1 are essential for retention. In contrast, a mutant PDI lacking the four cysteines in the two active sites still inhibits secretion, albeit less efficiently. PDI and ERp44 compete for Ero1 binding. PDI also prevents Ero1 aggregation and dimerization, thus chaperoning its own oxidase. This dynamic retention mechanism of Ero1 may be important for fine-tuning the regulation of ER redox homeostasis and quality control.

AB - Disulfide bonds are formed in the endoplasmic reticulum (ER) by sequential interchange reactions: Ero1α and Ero1β transfer oxidative equivalents to protein disulfide isomerase (PDI), which in turn oxidizes cargo proteins. Neither Ero1α nor Ero1β contains known ER localization motif (s), raising the question of how they are retained in this organelle. Here the authors show that, unlike endogenous molecules, overexpressed Ero1α and Ero1β are secreted by HeLa transfectants, suggesting saturation of their normal retention mechanism(s). Co-expression of either PDI or ERp44 prevents Ero1 secretion in a KDEL/RDEL dependent way. Covalent interactions between ERp44 and Ero1 are essential for retention. In contrast, a mutant PDI lacking the four cysteines in the two active sites still inhibits secretion, albeit less efficiently. PDI and ERp44 compete for Ero1 binding. PDI also prevents Ero1 aggregation and dimerization, thus chaperoning its own oxidase. This dynamic retention mechanism of Ero1 may be important for fine-tuning the regulation of ER redox homeostasis and quality control.

UR - http://www.scopus.com/inward/record.url?scp=33646699342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646699342&partnerID=8YFLogxK

U2 - 10.1089/ars.2006.8.274

DO - 10.1089/ars.2006.8.274

M3 - Article

C2 - 16677073

AN - SCOPUS:33646699342

VL - 8

SP - 274

EP - 282

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 3-4

ER -