Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain

Authors

  • Tomohiro Omura,

    1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba, Japan
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    • The first two authors contributed equally to this work.

  • Masayuki Kaneko,

    1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba, Japan
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    • The first two authors contributed equally to this work.

  • Naoki Tabei,

    1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba, Japan
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  • Yasunobu Okuma,

    Corresponding author
    1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba, Japan
    • Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba 288-0025, Japan
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  • Yasuyuki Nomura

    1. Department of Pharmacotherapeutics, Yokohama College of Pharmacy, Yokohama, Japan
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Abstract

HRD1 is an E3 ubiquitin ligase and plays an important role in endoplasmic reticulum-associated degradation (ERAD). Parkin-associated endothelin receptor-like receptor (Pael-R) is a substrate of the E3 ubiquitin ligase parkin, which has been implicated in ER stress-induced cell death in dopamine neurons in autosomal recessive juvenile parkinsonism (AR-JP). Recently, we demonstrated that endogenous HRD1 interacts with Pael-R, and that HRD1 promotes the degradation of Pael-R and protects cell death caused by the accumulation of Pael-R. Another group recently reported that HRD1 suppresses the toxicity of polyglutamine-expanded huntingtin. However, the topographical localization of HRD1 protein in the brain, especially related to neurodegenerative disease, is unclear. In this study, we used immunohistochemistry to investigate the topographical localization of HRD1 in the brain and demonstrated that HRD1 immunoreactivity was expressed widely in the substantia nigra pars compacta (SNC) containing dopaminergic neurons and was expressed in the cerebral cortex, hippocampus, dentate gyrus, striatum, globus pallidus, and Purkinje cells of the cerebellar cortex. Furthermore, HRD1 immunoreactivity was detected in the neuronal cells but not in the glial cells. These results suggest that HRD1 may play an important role in maintaining higher brain function, including motor function or learning and memory. In addition, HRD1 may have substrates other than Pael-R that are implicated in neurodegenerative disorders. © 2008 Wiley-Liss, Inc.

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