Updated on 2026/04/30

写真a

 
KURODA Keisuke
 
Organization
Graduate School of Medicine Program in Integrated Medicine Associate Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Associate Professor
External link

Degree 1

  1. Doctor of Philosophy (Medical Science) ( 2011.11   Nagoya University ) 

Research Interests 9

  1. DISC1

  2. Signal transduction

  3. dopamine

  4. schizophrenia

  5. Cell Biology

  6. Psychiatry

  7. Biochemistry

  8. 包括脳ネットワーク

  9. Small GTPase

Research Areas 5

  1. Life Science / Pharmacology

  2. Life Science / Cell biology

  3. Life Science / Psychiatry

  4. Life Science / Neuroscience - general

  5. Life Science / Molecular biology

Research History 6

  1. Nagoya University   School of Medicine Department of Medicine

    2026.4

  2. Nagoya University   Graduate School of Medicine

    2026.4

  3. Nagoya University   Graduate School of Medicine Program in Integrated Medicine   Associate Professor

    2025.4

  4. Nagoya University Graduate School of Medicine   Designated Associate Professor

    2021.4 - 2025.3

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  5. Nagoya University Graduate School of Medicine   Designated Assistant Professor

    2012.1 - 2021.3

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  6. Nagoya University Graduate School of Medicine   guest researcher

    2010.4 - 2011.12

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Education 4

  1. Nagoya University   Graduate School, Division of Medical Sciences

    2006.4 - 2010.3

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    Country: Japan

  2. Nagoya University   Graduate School of Medicine

    2006.4 - 2010.3

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  3. Nagoya University   Faculty of Medicine

    1998.4 - 2004.3

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    Country: Japan

  4. Nagoya University   School of Medicine

    1998.4 - 2004.3

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Professional Memberships 4

  1. Society for Neuroscience

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  2. THE JAPANESE SOCIETY FOR NEUROCHEMISTRY

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  3. THE JAPANESE PHARMACOLOGICAL SOCIETY

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  4. THE JAPAN NEUROSCIENCE SOCIETY

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Papers 62

  1. Balance between dopamine and adenosine signals regulates the PKA/Rap1 pathway in striatal medium spiny neurons. Reviewed International journal Open Access

    Xinjian Zhang, Taku Nagai, Rijwan Uddin Ahammad, Keisuke Kuroda, Shinichi Nakamuta, Takashi Nakano, Naoto Yukinawa, Yasuhiro Funahashi, Yukie Yamahashi, Mutsuki Amano, Junichiro Yoshimoto, Kiyofumi Yamada, Kozo Kaibuchi

    Neurochemistry international   Vol. 122   page: 8 - 18   2019.1

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    DOI: 10.1016/j.neuint.2018.10.008

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  2. Behavioral alterations associated with targeted disruption of exons 2 and 3 of the Disc1 gene in the mouse Reviewed

    Keisuke Kuroda, Shinnosuke Yamada, Motoki Tanaka, Michiro Iizuka, Hisashi Yano, Daisuke Mori, Daisuke Tsuboi, Tomoki Nishioka, Takashi Namba, Yukihiko Iizuka, Shimpei Kubota, Taku Nagai, Daisuke Ibi, Rui Wang, Atsushi Enomoto, Mayu Isotani-Sakakibara, Naoya Asai, Kazushi Kimura, Hiroshi Kiyonari, Takaya Abe, Akira Mizoguchi, Masahiro Sokabe, Masahide Takahashi, Kiyofumi Yamada, Kozo Kaibuchi

    HUMAN MOLECULAR GENETICS   Vol. 20 ( 23 ) page: 4666 - 4683   2011.12

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    DOI: 10.1093/hmg/ddr400

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  3. Signal flow in the NMDA receptor-dependent phosphoproteome regulates postsynaptic plasticity for aversive learning. International journal Open Access

    Yasuhiro Funahashi, Rijwan Uddin Ahammad, Xinjian Zhang, Emran Hossen, Masahiro Kawatani, Shinichi Nakamuta, Akira Yoshimi, Minhua Wu, Huanhuan Wang, Mengya Wu, Xu Li, Md Omar Faruk, Md Hasanuzzaman Shohag, You-Hsin Lin, Daisuke Tsuboi, Tomoki Nishioka, Keisuke Kuroda, Mutsuki Amano, Yukihiko Noda, Kiyofumi Yamada, Kenji Sakimura, Taku Nagai, Takayuki Yamashita, Shigeo Uchino, Kozo Kaibuchi

    Science signaling   Vol. 17 ( 853 ) page: eado9852   2024.9

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    Structural plasticity of dendritic spines in the nucleus accumbens (NAc) is crucial for learning from aversive experiences. Activation of NMDA receptors (NMDARs) stimulates Ca2+-dependent signaling that leads to changes in the actin cytoskeleton, mediated by the Rho family of GTPases, resulting in postsynaptic remodeling essential for learning. We investigated how phosphorylation events downstream of NMDAR activation drive the changes in synaptic morphology that underlie aversive learning. Large-scale phosphoproteomic analyses of protein kinase targets in mouse striatal/accumbal slices revealed that NMDAR activation resulted in the phosphorylation of 194 proteins, including RhoA regulators such as ARHGEF2 and ARHGAP21. Phosphorylation of ARHGEF2 by the Ca2+-dependent protein kinase CaMKII enhanced its RhoGEF activity, thereby activating RhoA and its downstream effector Rho-associated kinase (ROCK/Rho-kinase). Further phosphoproteomic analysis identified 221 ROCK targets, including the postsynaptic scaffolding protein SHANK3, which is crucial for its interaction with NMDARs and other postsynaptic scaffolding proteins. ROCK-mediated phosphorylation of SHANK3 in the NAc was essential for spine growth and aversive learning. These findings demonstrate that NMDAR activation initiates a phosphorylation cascade crucial for learning and memory.

    DOI: 10.1126/scisignal.ado9852

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  4. Dopamine drives neuronal excitability via KCNQ channel phosphorylation for reward behavior. Reviewed International journal Open Access

    Daisuke Tsuboi, Takeshi Otsuka, Takushi Shimomura, Md Omar Faruk, Yukie Yamahashi, Mutsuki Amano, Yasuhiro Funahashi, Keisuke Kuroda, Tomoki Nishioka, Kenta Kobayashi, Hiromi Sano, Taku Nagai, Kiyofumi Yamada, Anastasios V Tzingounis, Atsushi Nambu, Yoshihiro Kubo, Yasuo Kawaguchi, Kozo Kaibuchi

    Cell reports   Vol. 40 ( 10 ) page: 111309 - 111309   2022.9

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    Dysfunctional dopamine signaling is implicated in various neuropsychological disorders. Previously, we reported that dopamine increases D1 receptor (D1R)-expressing medium spiny neuron (MSN) excitability and firing rates in the nucleus accumbens (NAc) via the PKA/Rap1/ERK pathway to promote reward behavior. Here, the results show that the D1R agonist, SKF81297, inhibits KCNQ-mediated currents and increases D1R-MSN firing rates in murine NAc slices, which is abolished by ERK inhibition. In vitro ERK phosphorylates KCNQ2 at Ser414 and Ser476; in vivo, KCNQ2 is phosphorylated downstream of dopamine signaling in NAc slices. Conditional deletion of Kcnq2 in D1R-MSNs reduces the inhibitory effect of SKF81297 on KCNQ channel activity, while enhancing neuronal excitability and cocaine-induced reward behavior. These effects are restored by wild-type, but not phospho-deficient KCNQ2. Hence, D1R-ERK signaling controls MSN excitability via KCNQ2 phosphorylation to regulate reward behavior, making KCNQ2 a potential therapeutical target for psychiatric diseases with a dysfunctional reward circuit.

    DOI: 10.1016/j.celrep.2022.111309

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  5. NMDA-induced activation of the CaMKII-RhoA-Rho-kinase pathway regulates aversive learning

    Funahashi Yasuhiro, Ahammad Rijwan Uddin, Zhang Xinjian, Emran Hossen, Faruk Md. Omar, Wang Huanhuan, Wu Minhua, Xu Yifan, Tsuboi Daisuke, Nishioka Tomoki, Kuroda Keisuke, Amano Mutsuki, Sakimura Kenji, Uchino Shigeo, Yamada Kiyofumi, Nagai Taku, Kaibuchi Kozo

    Proceedings for Annual Meeting of The Japanese Pharmacological Society   Vol. 96   page: 2-B-P-109   2022

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    Glutamate induces Ca<sup>2+</sup> influx in neurons through NMDA receptors (NMDARs) and activates Ca<sup>2+</sup>-dependent protein kinases, including CaMKII, which play critical roles in synaptic plasticity and learning. However, how these kinases regulate synaptic plasticity and learning remains largely unknown. Here, we performed phosphoproteomics and identified 160 proteins including ArhGEF2 whose phosphorylation were promoted by NMDA. CaMKII phosphorylated ArhGEF2 and stimulated its RhoGEF activity. Aversive stimuli induced CaMKII-mediated ArhGEF2 phosphorylation and Rho-kinase/ROCK activation in the nucleus accumbens (NAc). Inhibition of Rho-kinase in the NAc attenuated aversive learning. We also screened Rho-kinase substrates and identified 221 proteins including Shank3 which links actin filaments with NMDARs and AMPA receptors via Dlgap3. The Rho-kinase-mediated phosphorylation of Shank3 increased its interaction with Dlgap3. Manipulation of Shank3 in the NAc regulated dendritic spine formation and aversive learning in a phosphorylation-dependent manner. These results demonstrate that NMDA activates the CaMKII-ArhGEF2-Rho-kinase pathway to induce Shank3 phosphorylation for aversive learning.

    DOI: 10.1254/jpssuppl.96.0_2-b-p-109

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  6. Accumbal D2R-medium spiny neurons regulate aversive behaviors through PKA-Rap1 pathway Reviewed International journal Open Access

    You-Hsin Lin, Yukie Yamahashi, Keisuke Kuroda, Md. Omar Faruk, Xinjian Zhang, Kiyofumi Yamada, Akihiro Yamanaka, Taku Nagai, Kozo Kaibuchi

    Neurochemistry International   Vol. 143   page: 104935 - 104935   2021.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier {BV}  

    DOI: 10.1016/j.neuint.2020.104935

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  7. Striatal TRPV1 activation by acetaminophen ameliorates dopamine D<inf>2</inf> receptor antagonist–induced orofacial dyskinesia Open Access

    Nagaoka, K., Nagashima, T., Asaoka, N., Yamamoto, H., Toda, C., Kayanuma, G., Siswanto, S., Funahashi, Y., Kuroda, K., Kaibuchi, K., Mori, Y., Nagayasu, K., Shirakawa, H., Kaneko, S.

    JCI Insight   Vol. 6 ( 10 )   2021

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    DOI: 10.1172/jci.insight.145632

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  8. ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk Reviewed International journal Open Access

    Sekiguchi, M., Sobue, A., Kushima, I., Wang, C., Arioka, Y., Kato, H., Kodama, A., Kubo, H., Ito, N., Sawahata, M., Hada, K., Ikeda, R., Shinno, M., Mizukoshi, C., Tsujimura, K., Yoshimi, A., Ishizuka, K., Takasaki, Y., Kimura, H., Xing, J., Yu, Y., Yamamoto, M., Okada, T., Shishido, E., Inada, T., Nakatochi, M., Takano, T., Kuroda, K., Amano, M., Aleksic, B., Yamomoto, T., Sakuma, T., Aida, T., Tanaka, K., Hashimoto, R., Arai, M., Ikeda, M., Iwata, N., Shimamura, T., Nagai, T., Nabeshima, T., Kaibuchi, K., Yamada, K., Mori, D., Ozaki, N.

    Translational Psychiatry   Vol. 10 ( 1 ) page: 247   2020

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    DOI: 10.1038/s41398-020-00917-z

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  9. Phosphorylation of Npas4 by MAPK Regulates Reward-Related Gene Expression and Behaviors. Reviewed International journal Open Access

    Yasuhiro Funahashi, Anthony Ariza, Ryosuke Emi, Yifan Xu, Wei Shan, Ko Suzuki, Sachi Kozawa, Rijwan Uddin Ahammad, Mengya Wu, Tetsuya Takano, Yoshimitsu Yura, Keisuke Kuroda, Taku Nagai, Mutsuki Amano, Kiyofumi Yamada, Kozo Kaibuchi

    Cell reports   Vol. 29 ( 10 ) page: 3235 - 3252   2019.12

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    Dopamine (DA) activates mitogen-activated protein kinase (MAPK) via protein kinase A (PKA)/Rap1 in medium spiny neurons (MSNs) expressing the dopamine D1 receptor (D1R) in the nucleus accumbens (NAc), thereby regulating reward-related behavior. However, how MAPK regulates reward-related learning and memory through gene expression is poorly understood. Here, to identify the relevant transcriptional factors, we perform proteomic analysis using affinity beads coated with cyclic AMP response element binding protein (CREB)-binding protein (CBP), a transcriptional coactivator involved in reward-related behavior. We identify more than 400 CBP-interacting proteins, including Neuronal Per Arnt Sim domain protein 4 (Npas4). We find that MAPK phosphorylates Npas4 downstream of PKA, increasing the Npas4-CBP interaction and the transcriptional activity of Npas4 at the brain-derived neurotrophic factor (BDNF) promoter. The deletion of Npas4 in D1R-expressing MSNs impairs cocaine-induced place preference, which is rescued by Npas4-wild-type (WT), but not by a phospho-deficient Npas4 mutant. These observations suggest that MAPK phosphorylates Npas4 in D1R-MSNs and increases transcriptional activity to enhance reward-related learning and memory.

    DOI: 10.1016/j.celrep.2019.10.116

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  10. Comprehensive analysis of kinase-oriented phospho-signalling pathways. Reviewed International journal Open Access

    Mutsuki Amano, Tomoki Nishioka, Daisuke Tsuboi, Keisuke Kuroda, Yasuhiro Funahashi, Yukie Yamahashi, Kozo Kaibuchi

    Journal of biochemistry   Vol. 165 ( 4 ) page: 301 - 307   2019.4

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    DOI: 10.1093/jb/mvy115

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  11. KANPHOS (Kinase-Associated Phospho-Signaling) Platform - A comprehensive database for kinase-associated neural phosphorylation signaling

    Kuroda Keisuke, Nagai Taku, Amano Mutsuki, Yoshimoto Junichiro, Kannon Takayuki, Nishioka Tomoki, Usui Shiro, Kaibuchi Kozo

    Proceedings for Annual Meeting of The Japanese Pharmacological Society   Vol. 92 ( 0 ) page: 1 - P-132   2019

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    <p>Protein phosphorylation is a major and essential post-translational modification in eukaryotic cells that plays a critical role in various cellular processes. While recent advances in mass spectrometry based proteomics allowed us to identify approximately 200,000 phosphorylation sites, it is not fully understood which sites are phosphorylated by a specific kinase and which extracellular stimuli regulate the protein phosphorylation via intracellular signaling cascades. Recently, we have developed an in vitro approach termed the kinase-interacting substrate screening (KISS) method and an in vivo approach termed kinase-oriented substrate screening (KIOSS) method. Using KIOSS method, we analyzed the phosphorylation signals downstream of dopamine in mouse striatal slices, and found that about 100 proteins including ion channels and transcription factors were phosphorylated probably by PKA or MAPK. Here, we present an on-line database system which provides the phosphorylation signals identified by our KISS and KIOSS methods as well as those previously reported in the literature. The database system and its web portal, named KANPHOS (Kinase-Associated PHOspho-Signaling), were built based on the Next Generation XooNIps. We also demonstrate how to retrieve proteins and pathways in striatal medium-sized spiny neurons modulated by extracellular dopaminergic stimulation.</p>

    DOI: 10.1254/jpssuppl.92.0_1-P-132

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  12. Cell type-specific activation of mitogen-activated protein kinase in D1 receptor-expressing neurons of the nucleus accumbens potentiates stimulus-reward learning in mice Reviewed International journal Open Access

    Bin Saifullah, Md. Ali, Nagai Taku, Kuroda Keisuke, Wulaer Bolati, Nabeshima Toshitaka, Kaibuchi Kozo, Yamada Kiyofumi

    Scientific Reports   Vol. 8 ( 1 ) page: 14413 - 14413   2018.12

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    DOI: 10.1038/s41598-018-32840-1

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  13. Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1<sup>Δ2-3/Δ2-3</sup> mice Reviewed Open Access

    Wulaer, B., Nagai, T., Sobue, A., Itoh, N., Kuroda, K., Kaibuchi, K., Nabeshima, T., Yamada, K.

    Genes, Brain and Behavior   Vol. 17 ( 8 )   2018.11

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    DOI: 10.1111/gbb.12478

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  14. IN VIVO IMAGING FOR THE EFFECT OF COCAINE

    Zhu Y., Ito N., Nagai T., Kuroda K., Kaibuchi K., Nabeshima T., Yamada K.

    ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH   Vol. 42   page: 28A-28A   2018.8

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  15. Dopamine-induced phosphorylation of NPAS4 through MAPK regulates reward-related learning and memory

    Funahashi Y., Ariza A., Suzuki K., Wei S., Kozawa S., Takano T., Kuroda K., Nagai T., Kaibuchi K.

    JOURNAL OF NEUROCHEMISTRY   Vol. 142   page: 129-129   2017.8

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  16. Phosphorylation signals in hippocampal and striatal synapses

    Kaibuchi K., Kuroda K., Yoshikawa M.

    JOURNAL OF NEUROCHEMISTRY   Vol. 142   page: 22-22   2017.8

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  17. KANPHOS(Kinase-Associated Phospho-Signaling)Platform 新規リン酸化DBプラットフォーム

    天野 睦紀, 西岡 朋生, 黒田 啓介, 吉本 潤一郎, 観音 隆幸, 臼井 支朗, 貝淵 弘三

    日本細胞生物学会大会講演要旨集   Vol. 69回   page: 83 - 83   2017.5

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  18. Neuropeptide Y neuronal network dysfunction in the frontal lobe of a genetic mouse model of schizophrenia Reviewed Open Access

    Shunsuke Morosawa, Shuji Iritani, Hiroshige Fujishiro, Hirotaka Sekiguchi, Youta Torii, Chikako Habuchi, Keisuke Kuroda, Kozo Kaibuchi, Norio Ozaki

    NEUROPEPTIDES   Vol. 62   page: 27 - 35   2017.4

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    DOI: 10.1016/j.npep.2016.12.010

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  19. RhoA activity regulates spine morphology and memory formation

    Nakanose Yuki, Kuroda Keisuke, Zhang Xinjian, Oda Kaishu, Nagai Taku, Kaibuchi Kozo

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 133 ( 3 ) page: S160-S160   2017.3

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  20. KANPHOS (Kinase-Associated Phospho-Signaling) Platform - A database for neural phosphoproteomics with quality control

    Kuroda Keisuke, Nagai Taku, Amano Mutsuki, Yoshimoto Junichiro, Kannon Takayuki, Nishioka Tomoki, Usui Shiro, Kaibuchi Kozo

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 133 ( 3 ) page: S263-S263   2017.3

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  21. Dopamine-induced phosphorylation of NPAS4 through MAPK regulates reward-related learning and memory

    Yasuhiro Funahashi, Ariza Anthony, Wei Shan, Kozawa Sachi, Okuda Keiichiro, Suzuki Ko, Takano Tetsuya, Yura Yoshimitsu, Kuroda Keisuke, Nagai Taku, Kaibuchi Kozo

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 133 ( 3 ) page: S216-S216   2017.3

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  22. Elevated repetitive and compulsive-like behavior in a schizophrenia animal model

    Wulaer Bolati, Nagai Taku, Sobue Akira, Kuroda Keisuke, Kaibuchi Kozo, Nabeshima Toshitaka, Yamada Kiyotumi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 133 ( 3 ) page: S219-S219   2017.3

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  23. Cell-type-specific isolation of 14-3-3 associated phosphoprotein from complex brain tissues

    Yoshikawa Marina, Kuroda Keisuke, Nagai Taku, Kaibuchi Kozo

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 133 ( 3 ) page: S159-S159   2017.3

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  24. The activity-dependent transcription factor NPAS4 regulates reward-related learning and memory

    Suzuki Ko, Funahashi Yasuhiro, Ariza Anthony, Wei Shan, Kuroda Keisuke, Nagai Taku, Kaibuchi Kozo

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 133 ( 3 ) page: S164-S164   2017.3

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  25. Cell-type-specific isolation of 14-3-3 associated phosphoprotein from complex brain tissues.

    Yoshikawa M., Kuroda K., Nagai T., Kaibuchi K.

    MOLECULAR BIOLOGY OF THE CELL   Vol. 28   page: .   2017

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  26. RhoA activity regulates spine morphology and memory associated behavior.

    Kuroda K., Zhang X., Oda K., Nakanose Y., Yoshikawa M., Nagai T., Kaibuchi K.

    MOLECULAR BIOLOGY OF THE CELL   Vol. 28   page: .   2017

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  27. Immunohistochemical evaluation of the GABAergic neuronal system in the prefrontal cortex of a DISC1 knockout mouse model of schizophrenia Reviewed

    Kentaro Umeda, Shuji Iritani, Hiroshige Fujishiro, Hirotaka Sekiguchi, Youta Torii, Chikako Habuchi, Keisuke Kuroda, Kozo Kaibuchi, Norio Ozaki

    SYNAPSE   Vol. 70 ( 12 ) page: 508 - 518   2016.12

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    DOI: 10.1002/syn.21924

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  28. Phosphorylation Signals in Striatal Medium Spiny Neurons Reviewed

    Taku Nagai, Junichiro Yoshimoto, Takayuki Kannon, Keisuke Kuroda, Kozo Kaibuchi

    TRENDS IN PHARMACOLOGICAL SCIENCES   Vol. 37 ( 10 ) page: 858 - 871   2016.10

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  29. Survival of corticostriatal neurons by Rho/Rho-kinase signaling pathway Reviewed

    Kenta Kobayashi, Hiromi Sano, Shigeki Kato, Keisuke Kuroda, Shinichi Nakamuta, Tadashi Isa, Atsushi Nambu, Kozo Kaibuchi, Kazuto Kobayashi

    NEUROSCIENCE LETTERS   Vol. 630   page: 45 - 52   2016.9

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    DOI: 10.1016/j.neulet.2016.07.020

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  30. Catecholaminergic neuronal network dysfunction in the frontal lobe of a genetic mouse model of schizophrenia Reviewed

    Shuji Iritani, Hirotaka Sekiguchi, Chikako Habuchi, Youta Torii, Keisuke Kuroda, Kozo Kaibuchi, Norio Ozaki

    ACTA NEUROPSYCHIATRICA   Vol. 28 ( 2 ) page: 117 - 123   2016.4

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    DOI: 10.1017/neu.2015.51

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  31. Dopamine D1 receptor stimulation leads to Rap1 activation as a reward signal in vivo. Reviewed Open Access

    Nagai T, Nakamuta S, Kuroda K, Nakauchi S, Nishioka T, Takano T, Xinjian Zhang, Kenta Kobayashi K, Miura M, Nishi A, Kobayashi K, Yamada K, Amano M, Kaibuchi K

    Neuron   Vol. 89 ( 3 ) page: 550 - 565   2016.2

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  32. Focused Proteomics Revealed a Novel Rho-kinase Signaling Pathway in the Heart Reviewed Open Access

    Yoshimitsu Yura, Mutsuki Amano, Mikito Takefuji, Tomohiro Bando, Kou Suzuki, Katsuhiro Kato, Tomonari Hamaguchi, Md. Hasanuzzaman Shohag, Tetsuya Takano, Yasuhiro Funahashi, Shinichi Nakamuta, Keisuke Kuroda, Tomoki Nishioka, Toyoaki Murohara, Kozo Kaibuchi

    CELL STRUCTURE AND FUNCTION   Vol. 41 ( 2 ) page: 105 - 120   2016

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    DOI: 10.1247/csf.16011

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    Other Link: http://orcid.org/0000-0002-6715-5125

  33. Stimulation of synaptic vesicle exocytosis by the mental disease gene DISC1 is mediated by N-type voltage-gated calcium channels Reviewed Open Access

    Willcyn Tang, Jervis Vermal Thevathasan, Qingshu Lin, Kim Buay Lim, Keisuke Kuroda, Kozo Kaibuchi, Marcel Bilger, Tuck Wah Soong, Marc Fivaz

    Frontiers in Synaptic Neuroscience   Vol. 8   page: 15   2016

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers Research Foundation  

    DOI: 10.3389/fnsyn.2016.00015

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    Other Link: http://orcid.org/0000-0002-6715-5125

  34. Impairment of molecular transport in a mouse model of Schizophrenia Reviewed

    D. Tsuboi, K. Kuroda, M. Tanaka, T. Namba, S. Taya, N. Ozaki, K. Kaibuchi

    JOURNAL OF NEUROCHEMISTRY   Vol. 134   page: 356 - 356   2015.8

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  35. Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin Reviewed Open Access

    Aya Muramatsu, Atsushi Enomoto, Takuya Kato, Liang Weng, Keisuke Kuroda, Naoya Asai, Masato Asai, Shinji Mu, Masahide Takahashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 463 ( 4 ) page: 999 - 1005   2015.8

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    DOI: 10.1016/j.bbrc.2015.06.049

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

    Daisuke Tsuboi, Keisuke Kuroda, Motoki Tanaka, Takashi Namba, Yukihiko Iizuka, Shinichiro Taya, Tomoyasu Shinoda, Takao Hikita, Shinsuke Muraoka, Michiro Iizuka, Ai Nimura, Akira Mizoguchi, Nobuyuki Shiina, Masahiro Sokabe, Hideyuki Okano, Katsuhiko Mikoshiba, Kozo Kaibuchi

    NATURE NEUROSCIENCE   Vol. 18 ( 5 ) page: 698 - +   2015.5

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    DOI: 10.1038/nn.3984

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  37. Disrupted-in-schizophrenia-1 (DISC1) Regulates Endoplasmic Reticulum Calcium Dynamics Reviewed Open Access

    Sung Jin Park, Jaehoon Jeong, Young-Un Park, Kyung-Sun Park, Haeryun Lee, Namgyu Lee, Sung-Mo Kim, Keisuke Kuroda, Minh Dang Nguyen, Kozo Kaibuchi, Sang Ki Park

    SCIENTIFIC REPORTS   Vol. 5   2015.3

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  38. Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin Reviewed Open Access

    Liang Weng, Atsushi Enomoto, Hiroshi Miyoshi, Kiyofumi Takahashi, Naoya Asai, Nobuhiro Morone, Ping Jiang, Jian An, Takuya Kato, Keisuke Kuroda, Takashi Watanabe, Masato Asai, Maki Ishida-Takagishi, Yoshiki Murakumo, Hideki Nakashima, Kozo Kaibuchi, Masahide Takahashi

    EMBO JOURNAL   Vol. 33 ( 18 ) page: 2098 - 2112   2014.9

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  39. Alterations of GABAergic and dopaminergic systems in mutant mice with disruption of exons 2 and 3 of the Disc1 gene Reviewed

    Tsuyoshi Nakai, Taku Nagai, Rui Wang, Shinnosuke Yamada, Keisuke Kuroda, Kozo Kaibuchi, Kiyofumi Yamada

    NEUROCHEMISTRY INTERNATIONAL   Vol. 74   page: 74 - 83   2014.7

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    DOI: 10.1016/j.neuint.2014.06.009

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  40. Neuronal Per Arnt Sim (PAS) Domain Protein 4 (NPAS4) Regulates Neurite Outgrowth and Phosphorylation of Synapsin I Reviewed Open Access

    Jaesuk Yun, Taku Nagai, Yoko Furukawa-Hibi, Keisuke Kuroda, Kozo Kaibuchi, Michael E. Greenberg, Kiyofumi Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 288 ( 4 ) page: 2655 - 2664   2013.1

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    DOI: 10.1074/jbc.M112.413310

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  41. Analysis of GABA system in DISC1 homozygous mutant mice Reviewed

    Nakai, T., Nagai, T., Yamada, S., Nakajima, A., Kuroda, K., Enomoto, A., Kaibuchi, K., Yamada, K.

    Society for Neuroscience Abstract Viewer and Itinerary Planner   Vol. 42   2012

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  42. Disrupted-In-Schizoprenia-1 regulates transport of neuronal mRNA Reviewed

    Tsuboi, D., Kuroda, K., Iizuka, Y., Okano, H., Mikoshiba, K., Kaibuchi, K.

    Society for Neuroscience Abstract Viewer and Itinerary Planner   Vol. 42   2012

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  43. Behavioral alterations associated with targeted disruption of the Disc1 gene in the mouse Reviewed

    Kuroda, K., Yamada, S., Tanaka, M., Sokabe, M., Yamada, K., Kaibuchi, K.

    Society for Neuroscience Abstract Viewer and Itinerary Planner   Vol. 42   2012

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  44. Girdin Is an Intrinsic Regulator of Neuroblast Chain Migration in the Rostral Migratory Stream of the Postnatal Brain Reviewed Open Access

    Yun Wang, Naoko Kaneko, Naoya Asai, Atsushi Enomoto, Mayu Isotani-Sakakibara, Takuya Kato, Masato Asai, Yoshiki Murakumo, Haruko Ota, Takao Hikita, Takashi Namba, Keisuke Kuroda, Kozo Kaibuchi, Guo-li Ming, Hongjun Song, Kazunobu Sawamoto, Masahide Takahashi

    JOURNAL OF NEUROSCIENCE   Vol. 31 ( 22 ) page: 8109 - 8122   2011.6

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    DOI: 10.1523/JNEUROSCI.1130-11.2011

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  45. Impairment of the tyrosine hydroxylase neuronal network in the orbitofrontal cortex of a genetically modified mouse model of schizophrenia Reviewed

    Hirotaka Sekiguchi, Shuji Iritani, Chikako Habuchi, Yohta Torii, Keisuke Kuroda, Kozo Kaibuchi, Norio Ozaki

    BRAIN RESEARCH   Vol. 1392   page: 47 - 53   2011.5

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    DOI: 10.1016/j.brainres.2011.03.058

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  46. Behavioral analysis of DISC1 knockout mice Reviewed

    Shinnosuke Yamada, Daisuke Ibi, Keisuke Kuroda, Rui Wang, Taku Nagai, Kozo Kaibuchi, Kiyofumi Yamada

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 115   page: 194P - 194P   2011

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  47. Proteomic analysis reveals novel binging partner of DISC1, a candidate risk gene of schizophrenia Reviewed

    Yukihiko Iizuka, Takafumi Kinoshita, Daisuke Tsuboi, Daisuke Mori, Keisuke Kuroda, Kozo Kaibuchi

    NEUROSCIENCE RESEARCH   Vol. 71   page: E300 - E300   2011

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  48. Npas4 regulates neurite outgrowth and phosphoryation of synapsin I Reviewed

    Jaesuk Yun, Taku Nagai, Yoko Hibi, Keisuke Kuroda, Kozo Kaibuchi, Kiyofumi Yamada

    NEUROSCIENCE RESEARCH   Vol. 71   page: E235 - E235   2011

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  49. Npas4 regulates neurite development and phosphoryation of synapsin I Reviewed

    Jaesuk Yun, Taku Nagai, Yoko Hibi, Keisuke Kuroda, Kozo Kaibuchi, Kiyofumi Yamada

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 115   page: 132P - 132P   2011

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  50. Histological investigation in the brain of genetically modified mouse of schizophrenia Reviewed

    Shuji Iritani, Hirotaka Sekiguchi, Chikako Habuchi, Yohta Torii, Keisuke Kuroda, Kozo Kaibuchi, Norio Ozaki

    NEUROSCIENCE RESEARCH   Vol. 71   page: E392 - E392   2011

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  51. Exploring the molecules interacting with Neuregulin1 cytoplasmic domain Reviewed

    Ryo Kuwata, Daisuke Mori, Daisuke Tsuboi, Tomoki Nishioka, Yukihiko Iizuka, Keisuke Kuroda, Hisashi Yano, Shinpei Kubota, Kozo Kaibuchi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 115   page: 143P - 143P   2011

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  52. Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi Reviewed Open Access

    Ken-ichiro Kubo, Kenji Tomita, Asuka Uto, Keisuke Kuroda, Saurav Seshadri, Jared Cohen, Kozo Kaibuchi, Atsushi Kamiya, Kazunori Nakajima

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 400 ( 4 ) page: 631 - 637   2010.10

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    DOI: 10.1016/j.bbrc.2010.08.117

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  53. Analysis of DISC1 using knockout mice and new antibodies Reviewed

    Kuroda, K., Mori, D., Namba, T., Tsuboi, D., Yano, H., Ibi, D., Tanaka, M., Isotani, M., Enomoto, A., Yamada, K., Sokabe, M., Takahashi, M., Kaibuchi, K.

    Society for Neuroscience Abstract Viewer and Itinerary Planner   Vol. 40   2010

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  54. The role of Npas4 in neurite outgrowth and phosphorylated synapsin I expression in Neuro2a cells and primary cultured hippocampal neurons Reviewed

    Jaesuk Yun, Taku Nagai, Yoko Hibi, Hiroyuki Koike, Atumi Nitta, Keisuke Kuroda, Kozo Kaibuchi, Kiyofumi Yamada

    NEUROSCIENCE RESEARCH   Vol. 68   page: E251 - E251   2010

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  55. Phenotypic analysis of DISC1 knockout mice Reviewed

    Keisuke Kuroda, Daisuke Mori, Shinichiro Taya, Daisuke Tsuboi, Takashi Namba, Ryo Kuwata, Hisashi Yano, Shinpei Kubota, Takafumi Kinoshita, Daisuke Ibi, Taku Nagai, Kiyofumi Yamada, Motoki Tanaka, Masahiro Sokabe, Mayu Isotani, Atsushi Enomoto, Masahide Takahashi, Hiroshi Kiyonari, Takaya Abe, Kozo Kaibuchi

    NEUROSCIENCE RESEARCH   Vol. 68   page: E200 - E200   2010

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  56. Npas4 regulates neuronal differentiation induced by lithium chloride in Neuro2a cells Reviewed

    Jaesuk Yu, Taku Nagai, Yoko Hibi, Hiroyuki Koike, Atumi Nitta, Keisuke Kuroda, Kozo Kaibuchi, Kiyofumi Yamada

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 112   page: 71P - 71P   2010

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  57. Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia-related protein Reviewed Open Access

    Takao Hikita, Shinichiro Taya, Yasutaka Fujino, Setsuko Taneichi-Kuroda, Kanae Ohta, Daisuke Tsuboi, Tomoyasu Shinoda, Keisuke Kuroda, Yusuke Funahashi, Junko Uraguchi-Asaki, Ryota Hashimoto, Kozo Kaibuchi

    JOURNAL OF NEUROCHEMISTRY   Vol. 110 ( 5 ) page: 1567 - 1574   2009.9

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    DOI: 10.1111/j.1471-4159.2009.06257.x

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  58. Roles of Disrupted-In-Schizophrenia 1-Interacting Protein Girdin in Postnatal Development of the Dentate Gyrus Reviewed Open Access

    Atsushi Enomoto, Naoya Asai, Takashi Namba, Yun Wang, Takuya Kato, Motoki Tanaka, Hitoshi Tatsumi, Shinichiro Taya, Daisuke Tsuboi, Keisuke Kuroda, Naoko Kaneko, Kazunobu Sawamoto, Rieko Miyamoto, Mayumi Jijiwa, Yoshiki Murakumo, Masahiro Sokabe, Tatsunori Seki, Kozo Kaibuchi, Masahide Takahashi

    NEURON   Vol. 63 ( 6 ) page: 774 - 787   2009.9

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    DOI: 10.1016/j.neuron.2009.08.015

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  59. Pathophysiological functions of DISC1 as a component of RNA granule Reviewed

    Daisuke Tsuboi, Keisuke Kuroda, Yasutaka Fujino, Kozo Kaibuchi

    NEUROSCIENCE RESEARCH   Vol. 65   page: S63 - S63   2009

  60. Regulation of DISC1 through phosphorylation by ERK Reviewed

    Keisuke Kuroda, Shinichiro Taya, Junko Uraguchi, Yusuke Funahashi, Kozo Kaibuchi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 106   page: 140P - 140P   2008

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  61. DISC1 regulates the transport of the NUDEL/LIS1/14-3-3 epsilon complex through Kinesin-1 Reviewed Open Access

    Shinichiro Taya, Tomoyasu Shinoda, Daisuke Tsuboi, Junko Asaki, Kumiko Nagai, Takao Hikita, Setsuko Kuroda, Keisuke Kuroda, Mariko Shimizu, Shinji Hirotsune, Akihiro Iwamatsu, Kozo Kaibuchi

    JOURNAL OF NEUROSCIENCE   Vol. 27 ( 1 ) page: 15 - 26   2007.1

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    DOI: 10.1523/JNEUROSCI.3826-06.2006

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  62. Regulation of DISC1 through phosphorylation by ERK Reviewed

    Shinichiro Taya, Junko Uraguchi-Asaki, Keisuke Kuroda, Kozo Kaibuchi

    NEUROSCIENCE RESEARCH   Vol. 58   page: S65 - S65   2007

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MISC 24

  1. リン酸化プロテオミクスが紐解く情動学習の分子基盤と精神疾患病態

    船橋靖広, 船橋靖広, UDDIN Ahammad Rijwan, 張心健, 河谷昌泰, 吉見陽, 坪井大輔, 坪井大輔, 西岡朋生, 西岡朋生, 黒田啓介, 野田幸裕, 山田清文, 崎村建司, 永井拓, 山下貴之, 内野茂夫, 貝淵弘三, 貝淵弘三

    次世代薬理学セミナー要旨集(Web)   Vol. 2025   2025

  2. NMDA受容体依存性のリン酸化プロテオームが忌避学習のための後シナプス形成を制御する

    船橋靖広, 船橋靖広, AHAMMAD Rijwan Uddin, AHAMMAD Rijwan Uddin, 張心健, HOSSEN Emran, HOSSEN Emran, 河谷昌泰, 吉見陽, 吉見陽, 呉敏華, 王緩緩, 王緩緩, 李旭, 李旭, 坪井大輔, 坪井大輔, 西岡朋生, 西岡朋生, 黒田啓介, 天野睦紀, 野田幸裕, 野田幸裕, 山田清文, 崎村建司, 永井拓, 山下貴之, 内野茂夫, 貝淵弘三, 貝淵弘三

    日本生物学的精神医学会(Web)   Vol. 46th   2024

  3. Unraveling the Phosphoprotein Network: Roles and Functions of NMDAR Cascades in Synaptic Growth and Learning

    船橋靖広, 船橋靖広, AHAMMAD Rijwan Uddin, AHAMMAD Rijwan Uddin, 張心健, EMRAN Hossen, EMRAN Hossen, 河谷昌泰, 吉見陽, 吉見陽, 呉敏華, 王緩緩, 王緩緩, 坪井大輔, 坪井大輔, 西岡朋生, 西岡朋生, 黒田啓介, 天野睦紀, 野田幸裕, 野田幸裕, 山田清文, 崎村建司, 永井拓, 山下貴之, 内野茂夫, 貝淵弘三, 貝淵弘三

    日本薬理学雑誌   Vol. 158 ( Supplement )   2023

  4. Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1Δ2-3/Δ2-3 mice. Reviewed

    Wulaer, B, Nagai T, Sobue, A, Itoh, N, Kuroda, K, Kaibuchi, K, Nabeshima, T, Yamada, K

    Gene Brain Behav     page: e12478   2018.4

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  5. To understand the molecular mechanism of psychiatric disorders. Analysis of dopaminergic intracellular signaling

    黒田啓介

    日本生物学的精神医学会誌   Vol. 28 ( 3 ) page: 127‐131 - 131   2017.9

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  6. Dopamine-induced phosphorylation of NPAS4 through MAPK regulates reward-related learning and memory

    Y. Funahashi, A. Ariza, K. Suzuki, S. Wei, S. Kozawa, T. Takano, K. Kuroda, T. Nagai, K. Kaibuchi

    JOURNAL OF NEUROCHEMISTRY   Vol. 142   page: 129 - 129   2017.8

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  7. Phosphorylation signals in hippocampal and striatal synapses

    K. Kaibuchi, K. Kuroda, M. Yoshikawa

    JOURNAL OF NEUROCHEMISTRY   Vol. 142   page: 22 - 22   2017.8

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  8. KANPHOS (Kinase-Associated Phospho-Signaling) Platform - A database for neural phosphoproteomics with quality control

    Keisuke Kuroda, Taku Nagai, Mutsuki Amano, Junichiro Yoshimoto, Takayuki Kannon, Tomoki Nishioka, Shiro Usui, Kozo Kaibuchi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 133 ( 3 ) page: S263 - S263   2017.3

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  9. Phosphorylation signals in striatal medium spiny neurons. Invited Reviewed

    Nagai, T, Yoshimoto, J, Kannon, T, Kuroda, K, Kaibuchi, K

    Trends Pharmacol. Sci.   Vol. 37   page: 858–871   2016.10

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  10. Dopamine phosphorylates GEF-H1 through PKA to regulate GEF-H 1 activity in striatum

    Xinjian Zhang, Keisuke Kuroda, Hiroyuki Takenaka, Kaishu Oda, Reon Kondo, Tomoki Nishioka, Shinichi Nakamuta, Taku Nagai, Kozo Kaibuchi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 130 ( 3 ) page: S194 - S194   2016.3

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  11. Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo Reviewed

    Taku Nagai, Shinichi Nakamuta, Keisuke Kuroda, Sakura Nakauchi, Tomoki Nishioka, Tetsuya Takano, Xinjian Zhang, Daisuke Tsuboi, Yasuhiro Funahashi, Takashi Nakano, Junichiro Yoshimoto, Kenta Kobayashi, Motokazu Uchigashima, Masahiko Watanabe, Masami Miura, Akinori Nishi, Kazuto Kobayashi, Kiyofumi Yamada, Mutsuki Amano, Kozo Kaibuchi

    Neuron   Vol. 89 ( 3 ) page: 550 - 565   2016.2

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    DOI: 10.1016/j.neuron.2015.12.019

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  12. 注目の遺伝子(第31回)統合失調症発症脆弱性分子DISC1の研究から明らかになった課題と新機能

    坪井 大輔, 森 大輔, 黒田 啓介

    分子精神医学   Vol. 15 ( 4 ) page: 301 - 303   2015.10

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    Other Link: http://search.jamas.or.jp/link/ui/2016055302

  13. 精神神経疾患の原因・関連遺伝子に関する基盤的開発研究

    星野幹雄, 貝淵弘三, 中島欽一, 岩本和也, 油谷浩幸, 内匠透, 松尾勲, 深田優子, 永井拓, 今吉格, 太田深秀, 井上高良, 須藤文和, 増山典久, 田谷真一郎, 山田真弓, 早瀬ヨネ子, 菅野幸江, 酒匂潤子, 井上由紀子, 一戸紀孝, 川口将史, 辻村啓太, 森大輔, 黒田啓介, 飯塚幸彦, JAESK Yun, 爪麻美

    精神・神経疾患研究開発費による研究報告集(2年度班・初年度班) 平成24年度     page: 390-405,438-439   2013

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  14. 疾患モデルと分子標的探索による治療薬開発 5.統合失調症の病因仮説とモデルマウス

    黒田啓介, 飯塚幸彦, 貝淵弘三

    実験医学   Vol. 30 ( 2 ) page: 377 - 381   2012.2

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  15. DISC1ノックアウトマウスにおけるGABAおよびドーパミン作動性神経系の解析

    中井剛, 永井拓, 王蕊, 山田真之亮, 黒田啓介, 貝淵弘三, 山田清文

    日本薬理学会近畿部会プログラム・要旨集   Vol. 122nd   page: 35   2012

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  16. DISC1ノックアウトマウスの行動薬理学的解析

    山田真之亮, 永井拓, 黒田啓介, 衣斐大祐, 王蕊, 貝淵弘三, 山田清文

    日本アルコール・薬物医学会雑誌   Vol. 46 ( 4 ) page: 131   2011.8

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  17. 新規蛍光Ca<sup>2+</sup>センサーG‐CaMP4を用いたレンチウイルスベクター遺伝子導入法による細胞内Ca<sup>2+</sup>動態の可視化

    中井剛, 永井拓, 榎本篤, 中牟田信一, 黒田啓介, 難波隆志, 日置寛之, 貝淵弘三, 中井淳一, 山田清文

    日本薬理学会近畿部会プログラム・要旨集   Vol. 120th   page: 56   2011

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  18. 高次脳機能におけるDISC1遺伝子の役割

    山田真之亮, 永井拓, 黒田啓介, 衣斐大祐, 王蕊, 貝淵弘三, 山田清文

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集   Vol. 21st-41st   page: 179   2011

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  19. 統合失調症発症脆弱因子DISC1の神経細胞における局在と機能解析

    久保田晋平, 森大輔, 黒田啓介, 坪井大輔, 貝淵弘三

    生化学     page: ROMBUNNO.2P-0958   2010

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  20. 統合失調症の神経発達障害とDISC1

    坪井大輔, 黒田啓介, 貝淵弘三

    医学のあゆみ   Vol. 231 ( 10 ) page: 1023 - 1027   2009.12

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  21. Pathophysiological functions of DISC1

      Vol. 231 ( 10 ) page: 1023 - 1027   2009.12

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  22. 統合失調症の分子精神医学 DISC1と統合失調症

    田谷真一郎, 黒田啓介, 貝淵弘三

    分子精神医学   Vol. 7 ( 4 ) page: 341 - 346   2007.10

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  23. DISC1と統合失調症 (特集 統合失調症の分子精神医学)

    田谷 真一郎, 黒田 啓介, 貝淵 弘三

    分子精神医学   Vol. 7 ( 4 ) page: 341 - 346   2007.10

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  24. NCAM結合タンパク質の同定

    黒田啓介, 中川誠人, 則竹淳, 西村隆, 深田優子, 深田正紀, 貝淵弘三

    日本細胞生物学会大会講演要旨集   Vol. 54th   page: 93   2001

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Presentations 2

  1. Cell-type-specific isolation of 14-3-3 associated phosphoprotein from complex brain tissues

    Yoshikawa, M; Kuroda, K; Nagai, T; Kaibuchi, K

    JOURNAL OF PHARMACOLOGICAL SCIENCES  2017.3 

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    Event date: 2017.3

    Language:Japanese   Presentation type:Poster presentation  

  2. Cell-type-specific isolation of 14-3-3 associated phosphoprotein from complex brain tissues. International conference

    Yoshikawa, M; Kuroda, K; Nagai, T; Kaibuchi, K

    MOLECULAR BIOLOGY OF THE CELL  2017 

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    Event date: 2017

    Language:English   Presentation type:Poster presentation  

KAKENHI (Grants-in-Aid for Scientific Research) 7

  1. Cell type specific analysis of intracellular signal in antipsychotics

    Grant number:20K07965  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

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  2. Analysis of RhoA/Rho-kinase signals in neuronal circuit

    Grant number:18K14816  2018.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    KURODA Keisuke

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    We analyzed the intracellular signaling of RhoA, a Rho family low molecular weight G protein, and its downstream molecule, Rho-kinase, in neurons. We found that the activator (GEF) and inactivator (GAP) of RhoA were phosphorylated in a neural activity-dependent manner. We observed changes in synaptic morphology and behavior in mice injected with AAV, which regulates the activity of RhoA and Rho-kinase, and in double-conditional knockout mice of Rho-kinase (Rock1 and Rock2). These findings suggest that neurons regulate synaptic morphology and behavior via RhoA and Rho-kinase signaling.

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  3. Study on regulatory mechanism of neural activity and emotional behavior by intracellular signals

    Grant number:17H01380  2017.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    Kaibuchi Kozo

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    Authorship:Coinvestigator(s) 

    In this study, we comprehensively identified proteins that are phosphorylated downstream of neuromodulators (dopamine, adenosine, acetylcholine) and glutamate using our proprietary phospho-proteomics method. We have elucidated the intracellular signal transduction that regulates neuronal excitatory, synaptic plasticity, and gene expression at the molecular level, and also elucidated the regulatory mechanism of emotional behavior and its learning & memory.

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  4. Elucidation of regulation mechanism of gene expression and emotional memory by dopamine signal

    Grant number:16K18393  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    Funahashi Yasuhiro, Kaibuchi Kozo, Nagai Taku, Amano Mutsuki, Nishioka Tomoki, Kuroda Keisuke

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    How dopamine regulates reward-related learning and memory through gene expression is poorly understood. Here, to identify the relevant transcriptional factors, we performed proteomic analysis using affinity beads coated with CREB-binding protein (CBP), a transcriptional coactivator involved in reward-related behavior. We identified more than 100 CBP-interacting proteins, including Neuronal Per-Arnt-Sim domain protein 4 (Npas4). We also found that MAPK phosphorylated Npas4 downstream of PKA, increasing Npas4-CBP interaction and the transcriptional activity of Npas4 at the brain-derived neurotrophic factor (BDNF) promoter. Deletion of Npas4 in the D1R-expressing MSNs impaired cocaine-induced place preference, which was rescued by Npas4-WT but not by a phospho-deficient Npas4 mutant. These observations suggest that MAPK phosphorylates Npas4 in D1R-MSNs and increases its transcriptional activity to enhance reward-related learning and memory.

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  5. Cell type specific analysis of intracellular signal in neural circuit

    Grant number:15K06772  2015.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kuroda Keisuke

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    Authorship:Principal investigator 

    Grant amount:\5200000 ( Direct Cost: \4000000 、 Indirect Cost:\1200000 )

    Dopamine activates PKA via D1 receptor / Gαs pathway in D1R-MSN of the nucleus accumbens. On the other hand, the adenosine / A2A receptor / Gαs pathway and the dopamine / D2 receptor / Gαi pathway are antagonized in D2R-MSN. The D2 receptor is constantly activated by dopamine, and when dopamine secretion decreases, repression is released and PKA is activated in D2R-MSN. Activated PKA phosphorylates and activates RasGRP2, which is an activator of Rap1 (GEF), and phosphorylates and inactivates Rap1GAP, which is an inactivator of Rap1 (GAP). PKA activates Rap1 / MAPK signals and enhances neuronal excitability.

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  6. Elucidation of phosphorylation signal regulating the cell polarity

    Grant number:25251021  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    Kaibuchi Kozo

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    The establishment and maintenance of cell polarity is essential to a wide range of biological processes, including axon formation and cell migration. In elucidating of molecular basis of cell polarization, cell polarity proteins such as PAR complex, and Scrib complex have been studied. In these studies, various kinases have been shown to act as cell polarity regulators. However, how these kinases regulate cell polarization is poorly understood. In this study, we used our recently developed proteomic system and identified numerous candidate substrates downstream of polarity-related kinases. Based on the substrate screening results, we analyzed the spatiotemporal dynamics and function of the identified substrates during cell migration. Recently, we also revealed how neurons can grow only a single axon while preventing the formation of unnecessary axons during neuronal polarization.

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  7. Re-evaluation of DISC1 using knockout mice and new antibodies

    Grant number:25830051  2013.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    KURODA Keisuke

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    Disrupted-In-Schizophrenia 1 (DISC1) is a promising candidate gene for susceptibility to psychiatric disorders, including schizophrenia. We previously generated a DISC1 knockout (KO) mouse and developed DISC1 antibodies. We found that no available antibodies to DISC1 without us recognized the endogenous DISC1. The DISC1 KO mouse displays no gross abnormalities, but it does show altered synaptic plasticity and abnormal emotional behaviors. So that we re-evaluate DISC1 using KO mice and new antibodies and investigate true function of DISC1 in synapse.
    We found that cell migration defect coused by DISC1 knockdown is an off-target effect of shRNA. This result suggests that DISC1 studies using DISC1 shRNAs should be interpreted with caution.
    We used proteomic analysis to screen for DISC1 interactors and identified several RNA-binding proteins. We found that DISC1 binds ITPR1 mRNA with HZF, thereby regulating its dendritic transport for synaptic plasticity.

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