title: Dynamic regulation of Ero1α and peroxiredoxin 4 localization in the secretory pathway.
abstract: In the early secretory compartment (ESC), a network of chaperones and enzymes assists oxidative folding of nascent proteins. Ero1 flavoproteins oxidize protein disulfide isomerase (PDI), generating H2O2 as a byproduct. Peroxiredoxin 4 (Prx4) can utilize luminal H2O2 to oxidize PDI, thus favoring oxidative folding while limiting oxidative stress. Interestingly, neither ER oxidase contains known ER retention signal(s), raising the question of how cells prevent their secretion. Here we show that the two proteins share similar intracellular localization mechanisms. Their secretion is prevented by sequential interactions with PDI and ERp44, two resident proteins of the ESC-bearing KDEL-like motifs. PDI binds preferentially Ero1α, whereas ERp44 equally retains Ero1α and Prx4. The different binding properties of Ero1α and Prx4 increase the robustness of ER redox homeostasis.
authors: From the Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8397, Japan.
authors: Taichi
authors: T
authors: Kakihana
authors: Kazutaka
authors: K
authors: Araki
authors: Stefano
authors: S
authors: Vavassori
authors: Shun-ichiro
authors: S
authors: Iemura
authors: Margherita
authors: M
authors: Cortini
authors: Claudio
authors: C
authors: Fagioli
authors: Tohru
authors: T
authors: Natsume
authors: Roberto
authors: R
authors: Sitia
authors: Kazuhiro
authors: K
authors: Nagata
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D055571:Secretory Pathway; D020349:Surface Plasmon Resonance
chemical_list: C451899:ERP44 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C405327:ERO1A protein, human; D010088:Oxidoreductases; C515980:PRDX4 protein, human; D054464:Peroxiredoxins; D019704:Protein Disulfide-Isomerases
keywords: Endoplasmic Reticulum (ER); Ero1; Oxidase; Peroxiredoxin; Prx4; Retention Mechanism; Thiol; Trafficking
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