2022/11/26 更新

写真a

ヤマダ セイヤ
山田 晴也
Scopus 論文情報  
論文数: 0  Citation: 0  h-index: 3

Citation Countは当該年に発表した論文の被引用数

所属
人間科学学術院 人間科学部
職名
助教

学歴

  • 2020年04月
    -
    2022年03月

    早稲田大学   人間科学研究科   健康・生命医科学研究領域 博士後期課程  

  • 2018年04月
    -
    2020年03月

    早稲田大学   人間科学研究科   健康・生命医科学研究領域 修士課程  

  • 2014年04月
    -
    2018年03月

    早稲田大学   人間科学部   人間情報科学科  

経歴

  • 2022年04月
    -
    継続中

    早稲田大学   人間科学学術院   助教

  • 2021年04月
    -
    2022年03月

    早稲田大学   人間科学学術院   助手

  • 2020年04月
    -
    2021年03月

    日本学術振興会 特別研究員DC1

  • 2020年04月
    -
    2021年03月

    早稲田大学   人間科学部   教育コーチ

所属学協会

  • 2018年04月
    -
    継続中

    日本神経科学学会

  • 2017年04月
    -
    継続中

    日本分子生物学会

 

研究分野

  • 神経科学一般

  • 分子生物学

研究キーワード

  • 大脳皮質発生、神経幹細胞、ニューロン新生、プリン代謝、プリノソーム、翻訳後修飾、ミトコンドリア

論文

  • Identification and expression profile of novel STAND gene Nwd2 in the mouse central nervous system

    Seiya Yamada, Ryutaro Furukawa, Shin-ichi Sakakibara

    Gene Expression Patterns   46   119284 - 119284  2022年12月  [査読有り]

    担当区分:筆頭著者, 責任著者

    DOI

    Scopus

  • Inka2, a novel Pak4 inhibitor, regulates actin dynamics in neuronal development

    Seiya Yamada, Tomoya Mizukoshi, Akinori Tokunaga, Shin-ichi Sakakibara

    PLOS Genetics   18 ( 10 ) e1010438 - e1010438  2022年10月  [査読有り]

    担当区分:筆頭著者

     概要を見る

    The actin filament is a fundamental part of the cytoskeleton defining cell morphology and regulating various physiological processes, including filopodia formation and dendritic spinogenesis of neurons. Serine/threonine-protein kinase Pak4, an essential effector, links Rho GTPases to control actin polymerization. Previously, we identified the Inka2 gene, a novel mammalian protein exhibiting sequence similarity to Inka1, which serves as a possible inhibitor for Pak4. Although Inka2 is dominantly expressed in the nervous system and involved in focal-adhesion dynamics, its molecular role remains unclear. Here, we found that Inka2-iBox directly binds to Pak4 catalytic domain to suppress actin polymerization. Inka2 promoted actin depolymerization and inhibited the formation of cellular protrusion caused by Pak4 activation. We further generated the conditional knockout mice of the Inka2 gene. The beta-galactosidase reporter indicated the preferential Inka2 expression in the dorsal forebrain neurons. Cortical pyramidal neurons of Inka2-/- mice exhibited decreased density and aberrant morphology of dendritic spines with marked activation/phosphorylation of downstream molecules of Pak4 signal cascade, including LIMK and Cofilin. These results uncovered the unexpected function of endogenous Pak4 inhibitor in neurons. Unlike Inka1, Inka2 is a critical mediator for actin reorganization required for dendritic spine development.

    DOI

    Scopus

  • Drp1 SUMO/deSUMOylation by Senp5 isoforms influences ER tubulation and mitochondrial dynamics to regulate brain development

    Seiya Yamada, Ayaka Sato, Naotada Ishihara, Hiroki Akiyama, Shin-ichi Sakakibara

    iScience   24 ( 12 ) 103484 - 103484  2021年12月  [査読有り]  [国際誌]

    担当区分:筆頭著者

     概要を見る

    Brain development is a highly orchestrated process requiring spatiotemporally regulated mitochondrial dynamics. Drp1, a key molecule in the mitochondrial fission machinery, undergoes various post-translational modifications including conjugation to the small ubiquitin-like modifier (SUMO). However, the functional significance of SUMOylation/deSUMOylation on Drp1 remains controversial. SUMO-specific protease 5 (Senp5L) catalyzes the deSUMOylation of Drp1. We revealed that a splicing variant of Senp5L, Senp5S, which lacks peptidase activity, prevents deSUMOylation of Drp1 by competing against other Senps. The altered SUMOylation level of Drp1 induced by Senp5L/5S affects mitochondrial morphology probably through controlling Drp1 ubiquitination and tubulation of the endoplasmic reticulum. A dynamic SUMOylation/deSUMOylation balance controls neuronal polarization and migration during the development of the cerebral cortex. These findings suggest a novel role of post-translational modification, in which deSUMOylation enzyme isoforms competitively regulate mitochondrial dynamics via Drp1 SUMOylation levels, in a tightly controlled process of neuronal differentiation and corticogenesis.

    DOI PubMed

    Scopus

    1
    被引用数
    (Scopus)
  • Nwd1 Regulates Neuronal Differentiation and Migration through Purinosome Formation in the Developing Cerebral Cortex

    Seiya Yamada, Ayaka Sato, Shin-ichi Sakakibara

    iScience   23 ( 5 ) 101058 - 101058  2020年05月  [査読有り]  [国際誌]

    担当区分:筆頭著者

     概要を見る

    Engagement of neural stem/progenitor cells (NSPCs) into proper neuronal differentiation requires the spatiotemporally regulated generation of metabolites. Purines are essential building blocks for many signaling molecules. Enzymes that catalyze de novo purine synthesis are assembled as a huge multienzyme complex called "purinosome." However, there is no evidence of the formation or physiological function of the purinosome in the brain. Here, we showed that a signal transduction ATPases with numerous domains (STAND) protein, NACHT and WD repeat domain-containing 1 (Nwd1), interacted with Paics, a purine-synthesizing enzyme, to regulate purinosome assembly in NSPCs. Altered Nwd1 expression affected purinosome formation and induced the mitotic exit and premature differentiation of NSPCs, repressing neuronal migration and periventricular heterotopia. Overexpression/knockdown of Paics or Fgams, other purinosome enzymes, in the developing brain resulted in a phenocopy of Nwd1 defects. These findings indicate that strict regulation of purinosome assembly/disassembly is crucial for maintaining NSPCs and corticogenesis.

    DOI PubMed

    Scopus

    9
    被引用数
    (Scopus)
  • Control of cell migration by the novel protein phosphatase-2A interacting protein inka2

    Hiroki Akiyama, Yumi Iwasaki, Seiya Yamada, Hiroyuki Kamiguchi, Shin-ichi Sakakibara

    Cell and Tissue Research   380 ( 3 ) 527 - 537  2020年01月  [査読有り]  [国際誌]

     概要を見る

    Cell migration is essential for many physiological and pathological processes, including embryonic development, wound healing, immune response and cancer metastasis. Inka2 transcripts are observed in migrating cells during embryonic development, suggesting the involvement of inka2 in cell migration. However, its precise role remains unclear. Here, we found that inka2 controlled focal adhesion dynamics and cell migration, likely by regulating protein phosphatase-2A (PP2A) function. A scratch assay revealed that inka2 shRNA-transfected NIH3T3 cells showed rapid wound closure, indicating an inhibitory effect by inka2 on cell migration. Live-cell imaging of NIH3T3 cells expressing EGFP-paxillin using total internal reflection fluorescence microscopy revealed that inka2 knockdown increased the turnover rate of focal adhesions. Given that PP2A, which consists of catalytic (C), regulatory (B) and scaffolding (A) subunits, is known to regulate focal adhesions, we examined the inka2-PP2A interaction. Immunoprecipitation revealed an association between inka2 and the PP2A C subunit. Binding of Inka2 to the C subunit prevented the association between the A and C subunits, suggesting that inka2 can inhibit PP2A function. Furthermore, both inka2 expression and PP2A inhibition decreased focal adhesion kinase-paxillin interaction, resulting in reduced formation of focal adhesions. We assessed the effect of pharmacological PP2A inhibition on the inka2 knockdown-induced increase in cell migration speed and found that treatment with a PP2A inhibitor negated the accelerated migration of inka2 knockdown cells. These results suggest that inka2 knockdown exerts its effects through PP2A-dependent regulation of focal adhesions. Our findings contribute to a better understanding of the molecular mechanisms underlying cell migration.

    DOI PubMed

    Scopus

    7
    被引用数
    (Scopus)
  • Expression profile of the STAND protein Nwd1 in the developing and mature mouse central nervous system

    Seiya Yamada, Shin-ichi Sakakibara

    Journal of Comparative Neurology (with cover page)   526 ( 13 ) 2099 - 2114  2018年09月  [査読有り]  [国際誌]

    担当区分:筆頭著者

     概要を見る

    The orchestrated events required during brain development, as well as the maintenance of adult neuronal plasticity, highly depend on the accurate responses of neuronal cells to various cellular stress or environmental stimuli. Recent studies have defined a previously unrecognized, broad class of multidomain proteins, designated as signal transduction ATPases with numerous domains (STAND), which comprises a large number of proteins, including the apoptotic peptidase activating factor 1 (Apaf1) and nucleotide-binding oligomerization domain-like receptors (NLRs), central players in cell death and innate immune responses, respectively. Although the involvement of STANDs in the central nervous system (CNS) has been postulated in terms of neuronal development and function, it remains largely unclear. Here, we identified Nwd1 (NACHT and WD repeat domain-containing protein 1), as a novel STAND protein, expressed in neural stem/progenitor cells (NSPCs). Structurally, Nwd1 was most analogous to the apoptosis regulator Apaf1, also involved in mitosis and axonal outgrowth regulation in the CNS. Using a specific antibody, we show that, during the embryonic and postnatal period, Nwd1 is expressed in nestin-positive NSPCs in vivo and in vitro, while postnatally it is found in terminally differentiated neurons and blood vessels. At the subcellular level, we demonstrate that Nwd1 is preferentially located in the cytosolic compartment of cultured NSPCs, partially overlapping with cytochrome c. These observations imply that Nwd1 might be involved in the neuronal lineage as a new STAND gene, including having a pro-apoptotic or nonapoptotic role, similar to Apaf1.

    DOI PubMed

    Scopus

    8
    被引用数
    (Scopus)

▼全件表示

受賞

  • FENS-IBRO/PERC Travel Grant Award

    2022年07月   FENS Forum 2022  

    受賞者: Seiya Yamada, Ayaka Sato, Shin-ichi Sakakibara

  • 小野梓記念賞 (学術賞)

    2020年03月   早稲田大学  

    受賞者: 山田晴也

  • 優秀発表賞

    2019年07月   NEURO2019(第42回日本神経科学大会/第62回神経化学会大会)  

    受賞者: 山田晴也, 秋山博紀, 榊原伸一

  • ジュニア研究者ポスター賞

    2018年07月   第41回日本神経科学大会  

    受賞者: 山田晴也, 秋山博紀, 榊原伸一

共同研究・競争的資金等の研究課題

  • Nwd1遺伝子によるプリノソーム形成を介した新たな神経分化機構の解明

    日本学術振興会  科学研究費助成事業 研究活動スタート支援

    研究期間:

    2021年08月
    -
    2023年03月
     

    山田 晴也

  • Nwd1遺伝子によるプリノソーム形成を介した新たな大脳皮質発生機構の解明

    日本学術振興会  特別研究員DC1

    研究期間:

    2020年04月
    -
    2021年03月
     

    山田晴也

講演・口頭発表等

  • 新規遺伝子Nwd1は大脳皮質発生を制御する

    山田 晴也, 秋山博紀, 榊原伸一

    Neuro2019(第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会)  

    発表年月: 2019年07月

    開催年月:
    2019年07月
     
     

学内研究費(特定課題)

  • プリノソーム形成に関与する新規遺伝子Nwd1のリガンド探索

    2021年   榊原伸一

     概要を見る

    正常な脳発達においてプリン代謝産物の産生量の制御は不可欠である。近年、プリン新生のための連続的な酵素反応は、巨大タンパク質複合体プリノソームで行われることが示された。プリノソームの形成は、細胞の増殖に必須の役割を持つと推定されるが、プリノソーム形成の分子メカニズムは不明である。申請者が新規同定したNwd1は神経幹細胞で豊富に発現し、プリノソーム形成に関与することで増殖を制御する。本研究ではプリノソーム形成におけるNwd1の役割を明らかにするため、Nwd1と相互作用するタンパク質群の同定を試みた。プルダウンアッセイとLC-MS解析の結果から、Nwd1と相互作用する因子群の同定に成功した。

 

現在担当している科目

担当経験のある科目(授業)

  • 現代の生命科学

    早稲田高等学院  

    2022年04月
    -
    継続中
     

  • ブレインサイエンス

    早稲田大学  

    2022年04月
    -
    継続中
     

  • ライフサイエンス研究法

    早稲田大学  

    2022年04月
    -
    継続中
     

  • ライフサイエンス入門(生体システム)

    早稲田大学  

    2022年04月
    -
    継続中