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Keratin inclusions alter cytosolic protein localization in hepatocytes

Authors

  • Shinichiro Hanada,

    Corresponding author
    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
      Dr Shinichiro Hanada, Division of Gastroenterology, Department of Medicine, Kurume University, School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Email: hanadas@med.kurume-u.ac.jp
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  • Masaru Harada,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
    2. Department of Medicine, Palo Alto Veterans Affairs Medical Center and Stanford University School of Medicine, Palo Alto, California, USA
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  • Takumi Kawaguchi,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
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  • Hiroto Kumemura,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
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  • Eitaro Taniguchi,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
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  • Hironori Koga,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
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  • Chikatoshi Yanagimoto,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
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  • Michiko Maeyama,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
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  • Takato Ueno,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
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  • Michio Sata

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan, and
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Dr Shinichiro Hanada, Division of Gastroenterology, Department of Medicine, Kurume University, School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Email: hanadas@med.kurume-u.ac.jp

Abstract

Aim:  Mallory bodies have been observed in various liver diseases, however, the precise mechanism and significance of these structures have yet to be determined.

Methods:  Previously we reported on the redistribution of cytosolic proteins to keratin inclusions in mutant keratin 18-transfected cells. In this study, we treated green fluorescent protein-tagged wild-type keratin 18-transfected cells with several proteasome inhibitors and performed immunofluorescent analyses.

Results:  Proteasome inhibitors induced intracellular keratin inclusions, and desmoplakin, zonula occludens-1 and β-catenin were relocated to keratin inclusions, while theintegral membrane proteins were intact. The cytosolic proteins, 14-3-3 ζ protein and glucose-6-phosphate dehydrogenase were also relocated to inclusions. Moreover, E-cadherin, a basolateral membrane protein, was present on both the apical and basolateral domains in inclusion-containing cells.

Conclusion:  These data are identical to those in the mutant keratin 18 transfection study and suggest that keratin inclusions induced by different treatments affect localization of various cytosolic components, which may influence cellular functions performed by these proteins.

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