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Nat Neurosci. 2015 May;18(5):698-707. doi: 10.1038/nn.3984. Epub 2015 Mar 30.

Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity.

Author information

1
1] Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan. [2] JST, CREST, Tokyo, Japan.
2
Department of Physiology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
3
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.
4
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.
5
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.
6
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
7
1] JST, CREST, Tokyo, Japan. [2] Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
8
Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
9
Department of Neuronal Cell Biology, Okazaki Institute for Integrative Bioscience and National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.
10
Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
11
Brain Science Institute, RIKEN, Wako, Saitama, Japan.

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.

PMID:
25821909
DOI:
10.1038/nn.3984
[Indexed for MEDLINE]

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