研究支援推進本部

西岡 朋生

ニシオカ トモキ  (Tomoki Nishioka)

基本情報

所属
藤田医科大学 総合医科学研究所 講師
学位
博士(理学)

researchmap会員ID
5000090739

論文

 61
  • 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 17(853) eado9852 2024年9月10日  
    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.
  • Takayuki Kannon, Satoshi Murashige, Tomoki Nishioka, Mutsuki Amano, Yasuhiro Funahashi, Daisuke Tsuboi, Yukie Yamahashi, Taku Nagai, Kozo Kaibuchi, Junichiro Yoshimoto
    Frontiers in Molecular Neuroscience 17 2024年4月2日  
    Protein phosphorylation, a key regulator of cellular processes, plays a central role in brain function and is implicated in neurological disorders. Information on protein phosphorylation is expected to be a clue for understanding various neuropsychiatric disorders and developing therapeutic strategies. Nonetheless, existing databases lack a specific focus on phosphorylation events in the brain, which are crucial for investigating the downstream pathway regulated by neurotransmitters. To overcome the gap, we have developed a web-based database named “Kinase-Associated Neural PHOspho-Signaling (KANPHOS).” This paper presents the design concept, detailed features, and a series of improvements for KANPHOS. KANPHOS is designed to support data-driven research by fulfilling three key objectives: (1) enabling the search for protein kinases and their substrates related to extracellular signals or diseases; (2) facilitating a consolidated search for information encompassing phosphorylated substrate genes, proteins, mutant mice, diseases, and more; and (3) offering integrated functionalities to support pathway and network analysis. KANPHOS is also equipped with API functionality to interact with external databases and analysis tools, enhancing its utility in data-driven investigations. Those key features represent a critical step toward unraveling the complex landscape of protein phosphorylation in the brain, with implications for elucidating the molecular mechanisms underlying neurological disorders. KANPHOS is freely accessible to all researchers at https://kanphos.jp.
  • 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 40(10) 111309-111309 2022年9月6日  
    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.
  • Tomoo Owa, Ryo Shiraishi, Toma Adachi, Satoshi Miyashita, Kentaro Ichijo, Tomoki Nishioka, Shinichiro Taya, Kozo Kaibuchi, Mikio Hoshino
    2022年8月17日  
    Abstract Granule cell progenitors (GCPs) and granule cells (GCs) in the cerebellum are excellent models for studying the differentiation of neural progenitors into neurons. Although gradual degradation of ATOH1 protein in GCPs leads to their differentiation into GCs, the underlying regulatory mechanism is unclear. We show that a homeodomain-less isoform of MEIS1 (MEIS1-HdL) regulates ATOH1 degradation and GCP differentiation in a transcriptional regulation-independent manner. BMP signaling phosphorylates Ser328 of ATOH1 via ERK. CUL3 was identified as an E3-ligase that polyubiquitinates Ser328 phosphorylated ATOH1, leading to ATOH1 degradation. MEIS1-HdL and full-length MEIS1 form a trimeric complex with CUL3 and COP9 signalosome that inhibits ATOH1 ubiquitination and degradation. MEIS1-HdL is exclusively expressed in GCPs and suppresses ATOH1 degradation and GCP differentiation into GCs, despite high BMP signaling activities in the cells. Our study provides insight into the precise regulatory machinery of the degradation of the pivotal protein ATOH1 and differentiation of neural progenitors.
  • Tomoo Owa, Ryo Shiraishi, Toma Adachi, Satoshi Miyashita, Kentaro Ichijo, Tomoki Nishioka, Shinichiro Taya, Kozo Kaibuchi, Mikio Hoshino
    2022年8月17日  
    Abstract Granule cell progenitors (GCPs) and granule cells (GCs) in the cerebellum are excellent models for studying the differentiation of neural progenitors into neurons. Although gradual degradation of ATOH1 protein in GCPs leads to their differentiation into GCs, the underlying regulatory mechanism is unclear. We show that a homeodomain-less isoform of MEIS1 (MEIS1-HdL) regulates ATOH1 degradation and GCP differentiation in a transcriptional regulation-independent manner. BMP signaling phosphorylates Ser328 of ATOH1 via ERK. CUL3 was identified as an E3-ligase that polyubiquitinates Ser328 phosphorylated ATOH1, leading to ATOH1 degradation. MEIS1-HdL and full-length MEIS1 form a trimeric complex with CUL3 and COP9 signalosome that inhibits ATOH1 ubiquitination and degradation. MEIS1-HdL is exclusively expressed in GCPs and suppresses ATOH1 degradation and GCP differentiation into GCs, despite high BMP signaling activities in the cells. Our study provides insight into the precise regulatory machinery of the degradation of the pivotal protein ATOH1 and differentiation of neural progenitors.

MISC

 14

共同研究・競争的資金等の研究課題

 5
  • 日本学術振興会 科学研究費助成事業 2017年4月 - 2021年3月
    貝淵 弘三, 永井 拓, 天野 睦紀, 西岡 朋生, 黒田 啓介, 船橋 靖広
  • 日本学術振興会 科学研究費助成事業 2013年4月 - 2016年3月
    貝淵 弘三, 西岡 朋生, 天野 睦紀, 黒田 啓介, 中牟田 信一, 渡辺 崇
  • 日本学術振興会 科学研究費助成事業 2010年4月 - 2016年3月
    木村 實, 丹治 順, 高田 昌彦, 中村 克樹, 大塚 稔久, 青木 茂樹, 高尾 英正, 下地 啓五, 後藤 政実, 吉浦 敬, 中田 安浩, 阿部 修, 増本 智彦, 徳丸 阿耶, 松村 明, 桐野 衛二, 寺田 一志, 佐藤 典子, 笠井 清登, 橋本 亮太, 丹羽 真一, 加藤 忠史, 鈴木 道雄, 入谷 修司, 根本 清貴, 富田 博秋, 村山 繁雄, 赤津 裕康, 高尾 昌樹, 齊藤 祐子, 尾藤 晴彦, 吉村 由美子, 松崎 政紀, 古田 寿昭, 岡戸 晴生, 斎藤 泉, 貝淵 弘三, 長谷川 成人, 饗場 篤, 椎名 伸之, 五十嵐 道弘, 西岡 朋生, 渡辺 雅彦, 小池 正人, 阪上 洋行, 重本 隆一, 深澤 有吾, 﨑村 建司, 森 寿, 三品 昌美, 小林 和人, 柳川 右千夫, 上村 匡, 石原 健, 能瀬 聡直, 飯野 雄一, 宮川 剛, 高雄 啓三, 虫明 元, 片山 統裕, 田中 徹, 井上 和秀, 岡部 繁男, 狩野 方伸, 藤山 文乃, 伊佐 正, 影山 龍一郎, 藤田 一郎, 吉田 明, 西川 徹, 貫名 信行, 深井 朋樹, 岩坪 威, 山森 哲雄, 岡澤 均, 田中 啓治, 柿木 隆介, 津田 一郎, 北澤 茂, 銅谷 賢治, 高橋 良輔, 池中 一裕, 祖父江 元, 長谷川 寿一, 太田 順, 齊藤 実, 門松 健治, 喜田 聡, 真鍋 俊也, 富田 泰輔, 岩田 淳, 村上 郁也, 筒井 健一郎, 花川 隆, 平井 宏和, 美馬 達哉, 礒村 宜和, 鮫島 和行, 星 英司, 宮田 麻理子, 柚崎 通介, 田中 真樹, 深田 正紀, 鈴木 匡子, 久場 博司, 桝 正幸, 木下 専, 杉原 泉, 白根 道子, 山本 亘彦, 西条 寿夫, 南部 篤, 内匠 透, 山下 俊英, 桜井 武, 玉巻 伸章, 畠 義郎, 原田 彰宏, 尾崎 紀夫, 坂井 克之, 久保 義弘, 中澤 敬信, 田中 謙二, 武井 延之, 等 誠司, 加藤 隆弘, 加藤 総夫, 白尾 智明, 泰羅 雅登, 岡野 栄之, 関野 祐子, 岡本 泰昌, 小松 英彦, 宮田 卓樹, 高橋 淑子, 西田 眞也, 富永 真琴, 寺田 一志
  • 日本学術振興会 科学研究費助成事業 2008年 - 2012年
    貝淵 弘三, 天野 睦紀, 渡辺 崇, 森 大輔, 西岡 朋生, 坪井 大輔, 有村 奈利子
  • 日本学術振興会 科学研究費助成事業 2005年 - 2009年
    貝淵 弘三, 有村 奈利子, 森 大輔, 西岡 朋生

その他

 1
  • 質量分析装置を用いた組織、細胞レベルの網羅的in vivoリン酸化シグナルネットワーク解析技術(KIOSS: Nishioka et.al., Curr Protoc Chem Biol. 2019 Mar;11(1):e60. doi: 10.1002/cpch.60.) *本研究シーズに関する産学共同研究の問い合わせは藤田医科大学産学連携推進セン ター(fuji-san@fujita-hu.ac.jp)まで