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

Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 9809671 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1726 (Electronic) Linking ISSN: 10976256 NLM ISO Abbreviation: Nat Neurosci Subsets: MEDLINE

Publication: <2002->: New York, NY : Nature Publishing Group
Original Publication: New York, NY : Nature America Inc., c1998-

Hippocampus/*metabolism ; Inositol 1,4,5-Trisphosphate Receptors/*genetics ; Nerve Tissue Proteins/*physiology ; Neuronal Plasticity/*physiology ; Proteins/*physiology ; RNA, Messenger/*metabolism ; RNA-Binding Proteins/*physiology; 3' Untranslated Regions/genetics ; Animals ; Biological Transport ; Cytoplasmic Granules/metabolism ; Dendrites/metabolism ; Dendrites/ultrastructure ; Hippocampus/cytology ; Humans ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/deficiency ; Nerve Tissue Proteins/genetics ; Neuronal Plasticity/genetics ; Protein Binding ; Protein Interaction Mapping ; RNA Interference ; RNA-Binding Proteins/genetics ; Recombinant Fusion Proteins/metabolism

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.

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0 (3' Untranslated Regions)
0 (DISC1 protein, human)
0 (Disc1 protein, mouse)
0 (Inositol 1,4,5-Trisphosphate Receptors)
0 (Itpr1 protein, mouse)
0 (Nerve Tissue Proteins)
0 (Proteins)
0 (RNA, Messenger)
0 (RNA-Binding Proteins)
0 (Recombinant Fusion Proteins)
0 (Zfp385 protein, mouse)

Date Created: 20150331 Date Completed: 20150709 Latest Revision: 20220330

20221213

10.1038/nn.3984

25821909