TY - JOUR
T1 - Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity
AU - Tsuboi, Daisuke
AU - Kuroda, Keisuke
AU - Tanaka, Motoki
AU - Namba, Takashi
AU - Iizuka, Yukihiko
AU - Taya, Shinichiro
AU - Shinoda, Tomoyasu
AU - Hikita, Takao
AU - Muraoka, Shinsuke
AU - Iizuka, Michiro
AU - Nimura, Ai
AU - Mizoguchi, Akira
AU - Shiina, Nobuyuki
AU - Sokabe, Masahiro
AU - Okano, Hideyuki
AU - Mikoshiba, Katsuhiko
AU - Kaibuchi, Kozo
N1 - Funding Information:
We gratefully acknowledge T. Takumi (Hiroshima University, Higashihiroshima, Japan) for providing rat Staufen cDNA, S. Okabe (University of Tokyo, Tokyo, Japan) for providing the pAct expression vector, H. Song (Johns Hopkins University school of Medicine, Baltimore, Maryland) for providing the Disc1 shRNA vector and K. Kosik (University of California, Santa Barbara, Santa Barbara, California) for providing the RSV-MS2-CAMK2A 3′ UTR construct. We thank T. Fujiwara (Kobe University) and A. Sawa (Johns Hopkins University) for helpful discussions. We also thank Y. Funahashi, Y. Fujino, H. Yano and T. Watanabe for providing materials; K. Kobayash and S. Suzuki for technical assistance; and T. Ishii for secretarial assistance. This work was supported in part by a Grant-in-Aid for the Strategic Research Program for Brain Science (SRPBS; Theme G) (26-J-JG38), a Grant-in-Aid for Scientific Research (S) (20227006), an Academic Frontier Project from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and a Grant-in-Aid for Creative Scientific Research from the Japan Society for the Promotion of Science, Japan Science and Technology Agency, CREST (26-J-Jc08).
Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
PY - 2015/4/28
Y1 - 2015/4/28
N2 - 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.
AB - 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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U2 - 10.1038/nn.3984
DO - 10.1038/nn.3984
M3 - Article
C2 - 25821909
AN - SCOPUS:84928705971
SN - 1097-6256
VL - 18
SP - 698
EP - 707
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 5
ER -