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. © Mary Ann Liebert, Inc.

Dynamic retention of Ero1α and Ero1β in the endoplasmic reticulum by interactions with PDI and ERp44 / M. Otsu, G. Bertoli, C. Fagioli, E. Guerini-Rocco, S. Nerini-Molteni, E. Ruffato, R. Sitia. - In: ANTIOXIDANTS & REDOX SIGNALING. - ISSN 1523-0864. - 8:3-4(2006 Mar), pp. 274-282.

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

G. Bertoli
Secondo
;
E. Guerini-Rocco;S. Nerini-Molteni;
2006

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. © Mary Ann Liebert, Inc.
No
English
Binding Sites; Binding, Competitive; Blotting, Western; Cysteine; Genetic Vectors; HeLa Cells; Humans; Membrane Glycoproteins; Membrane Proteins; Molecular Chaperones; Oxidation-Reduction; Oxidoreductases; Oxidoreductases Acting on Sulfur Group Donors; Plasmids; Protein Binding; Protein Disulfide-Isomerases; Transfection; Biochemistry
Settore BIO/11 - Biologia Molecolare
Articolo
Esperti anonimi
Pubblicazione scientifica
mar-2006
Liebert
8
3-4
274
282
9
Pubblicato
Periodico con rilevanza internazionale
scopus
pubmed
crossref
NON aderisco
info:eu-repo/semantics/article
Dynamic retention of Ero1α and Ero1β in the endoplasmic reticulum by interactions with PDI and ERp44 / M. Otsu, G. Bertoli, C. Fagioli, E. Guerini-Rocco, S. Nerini-Molteni, E. Ruffato, R. Sitia. - In: ANTIOXIDANTS & REDOX SIGNALING. - ISSN 1523-0864. - 8:3-4(2006 Mar), pp. 274-282.
none
Prodotti della ricerca::01 - Articolo su periodico
7
262
Article (author)
si
M. Otsu, G. Bertoli, C. Fagioli, E. Guerini-Rocco, S. Nerini-Molteni, E. Ruffato, R. Sitia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/515337
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