title: Establishment of a system for monitoring endoplasmic reticulum redox state in mammalian cells.
abstract: The endoplasmic reticulum (ER) performs a critical role in the oxidative folding of nascent proteins, such that perturbations to ER homeostasis may lead to protein misfolding and subsequent pathological processes. Among the mechanisms for maintaining ER homeostasis is a redox regulation, which is a critical determinant of the fate of ER-stressed cells. Here, we report the establishment of a system for monitoring the ER redox state in mammalian cells. The new ER redox-sensing system was developed based on the previously described monitoring system in yeast. Our system could successfully monitor the dynamic ER redox state in mammalian cells. Using this system, we find that manipulation of ER oxidases changes the ER redox state. The mammalian ER redox-sensing system could be used to study the mechanisms of ER redox regulation and provide a foundation for an approach to develop novel therapeutic modalities for human diseases related to dysregulated ER homeostasis including diabetes, neurodegeneration, and Wolfram syndrome.
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine and Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Kanekura
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ishigaki
authors.forename: Philip I
authors.initials: PI
authors.lastname: Merksamer
authors.forename: Feroz R
authors.initials: FR
authors.lastname: Papa
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Urano
mesh_terms: D000818:Animals; D002460:Cell Line; D003199:Computer Systems; D003920:Diabetes Mellitus / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism; D010084:Oxidation-Reduction; D017510:Protein Folding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014929:Wolfram Syndrome / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins
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