title: The origins of rimmed vacuoles and granulovacuolar degeneration bodies are associated with the Wnt signaling pathway.
abstract: Inclusion-body myositis (IBM) and Alzheimer's disease (AD) are biochemically characterized by the presence of aggregated β-amyloid protein and tau protein. In addition, both diseases are pathologically characterized by vacuolar changes, including rimmed vacuoles (RVs) in IBM and granulovacuolar degeneration (GVD) in AD. Previously, we demonstrated that RVs and GVD bodies are associated with a set of common molecules, leading us to speculate that both RVs and GVD bodies originate from similar structures on the plasma membrane of muscle cells and neuronal cells, namely, the neuromuscular junction (NMJ) and the postsynaptic spine especially in terms of Wnt signaling pathway. In this study, we investigated the presence of components of NMJ in RVs and/or postsynaptic spine in GVD bodies respectively by immunohistochemistry and immunofluorescence. The antigens probed included the following: (1) dishevelled (Dvl) family proteins (Dvl1, Dvl2 and Dvl3), (2) NMJ-associated proteins (low density lipoprotein-related protein 4 [Lrp4], heat shock protein 70 [Hsp70], β-catenin, phospho-β-catenin, rapsyn, P21-activated kinase 1 [PAK1], adenomatous polyposis coli [APC] and ADP-ribosylation factor 6 [Arf6]), (3) a lipid raft-associated molecule (phosphatidylinositol 4, 5-bisphosphate [PIP2]), and (4) other proteins [prion, glycogen-synthase kinase 3β (GSK-3β)]. In all cases of sporadic IBM examined, RVs were immunopositive for Dvl3, Hsp70, β-catenin, PIP2, APC, prion and GSK-3β. In all cases of AD examined, GVD bodies were immunopositive for Dvl3, phospho-β-catenin, rapsyn, APC and PIP2. These findings show that RVs and GVD bodies share common molecules associated with the Wnt signaling pathway, indicating that these structures share a common structural and functional origin.
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551 Hiroshima, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Murata-Shinozaki
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551 Hiroshima, Japan. Electronic address: tetakaha@hiroshima-u.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551 Hiroshima, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551 Hiroshima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: Department of Clinical Neuroscience, Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima, Tokushima, Japan.
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551 Hiroshima, Japan; JCHO, Hoshigaoka Medical Center, Hirakata, Osaka, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D049229:Dendritic Spines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D008875:Middle Aged; D018979:Myositis, Inclusion Body / Q000378:metabolism / Q000473:pathology; D009469:Neuromuscular Junction / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway
keywords: Alzheimer’s disease; Granulovacuolar degeneration; Inclusion-body myositis; Rimmed vacuole; Wnt