Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain.
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.
Omura
Tomohiro
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba, Japan.
Kaneko
Masayuki
M
Tabei
Naoki
N
Okuma
Yasunobu
Y
Nomura
Yasuyuki
Y
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
C498235:Syvn1 protein, mouse; D044767:Ubiquitin-Protein Ligases