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 language | English |
|---|---|
| Pages (from-to) | 274-282 |
| Number of pages | 9 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 8 |
| Issue number | 3-4 |
| DOIs | |
| Publication status | Published - Mar 2006 |
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ASJC Scopus subject areas
- Biochemistry
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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 journal › Article
}
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.
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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 -