title: Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity.
abstract: Disrupted-in-schizophrenia 1 (DISC1) is a susceptibility gene for major psychiatric disorders, including schizophrenia. DISC1 has been implicated in neurodevelopment in relation to scaffolding signal complexes. Here we used proteomic analysis to screen for DISC1 interactors and identified several RNA-binding proteins, such as hematopoietic zinc finger (HZF), that act as components of RNA-transporting granules. HZF participates in the mRNA localization of inositol-1,4,5-trisphosphate receptor type 1 (ITPR1), which plays a key role in synaptic plasticity. DISC1 colocalizes with HZF and ITPR1 mRNA in hippocampal dendrites and directly associates with neuronal mRNAs, including ITPR1 mRNA. The binding potential of DISC1 for ITPR1 mRNA is facilitated by HZF. Studies of Disc1-knockout mice have revealed that DISC1 regulates the dendritic transport of Itpr1 mRNA by directly interacting with its mRNA. The DISC1-mediated mRNA regulation is involved in synaptic plasticity. We show that DISC1 binds ITPR1 mRNA with HZF, thereby regulating its dendritic transport for synaptic plasticity.
authors.affiliation: 1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] JST, CREST, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuboi
authors.affiliation: 1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] JST, CREST, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Department of Physiology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: 1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] JST, CREST, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Namba
authors.affiliation: 1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] JST, CREST, Tokyo, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Iizuka
authors.affiliation: 1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] JST, CREST, Tokyo, Japan. [3] Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, Kodaira, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Taya
authors.affiliation: 1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] Department of Anatomy and Cell Biology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Shinoda
authors.affiliation: 1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] Department of Developmental and Regenerative Biology, Graduate School of Medical Science, Nagoya City University, Nagoya, Aichi, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hikita
authors.affiliation: Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Muraoka
authors.affiliation: 1] JST, CREST, Tokyo, Japan. [2] Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Michiro
authors.initials: M
authors.lastname: Iizuka
authors.affiliation: Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Nimura
authors.affiliation: Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.affiliation: Department of Neuronal Cell Biology, Okazaki Institute for Integrative Bioscience and National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shiina
authors.affiliation: Department of Physiology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Masahiro
authors.identifier: 0000000177910166
authors.initials: M
authors.lastname: Sokabe
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.affiliation: 1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] JST, CREST, Tokyo, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D003594:Cytoplasmic Granules / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011506:Proteins / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C412476:DISC1 protein, human; C498794:Disc1 protein, mouse; D053496:Inositol 1,4,5-Trisphosphate Receptors; C025389:Itpr1 protein, mouse; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C404217:Zfp385 protein, mouse
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