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神経成長における超解像度レベルの脂質ドメイン可視化とその構成脂質特性の解析

Publicly Offered Research

Project AreaQuality of lipids in biological systems
Project/Area Number 18H04670
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Research InstitutionNiigata University

Principal Investigator

五十嵐 道弘  新潟大学, 医歯学系, 教授 (50193173)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords脂質ラフト / 脂肪酸合成 / 超解像度顕微鏡 / リピドミクス / 成長円錐 / 小胞体 / 極長鎖脂肪酸
Outline of Annual Research Achievements

1) GPSN2-KOを作成し、解析したところ、胎生9.5日齢にて致死であることが判明した。変化は大きく分けて、神経系と循環器系(血管、心臓)の変化が中心と考えられた。神経系ではヘテロ胚の解析から、、末梢神経系の回路形成障害が認められ、軸索ガイダンスの障害が想定された。一方、循環器系統では、心臓の形成不全が生じていた。病理学的解析を行ったところ、心臓においては酸化ストレスの増大の可能性が認められた。これは極長鎖不飽和脂肪酸の形成不全により、酸化ストレスの消去システムが低下する可能性がある、このマウスの想定される特性に合致していた。またこのマウスのKOと、脂肪酸鎖長伸長の代謝ループ内にある酵素Hsd17b12のKO(2010年に報告)とは表現型が類似していることが判明した。リピドミクスに関して、まずP0時のヘテロ個体の解析で、野生型個体に比較して、脳では明らかに膜リン脂質の合成減少が見られた。一方、心臓などを含む部分ではさほどの変化は認められていなかった。9.5日胚ではホモ個体では、上記変化のほか、極長鎖脂肪酸を含むセラミド合成が障害されている結果を得た。
2) 脂質ラフトタンパク質GPM6aのTgマウスを含む、E-MARS法の単離脂質ラフト画分によるプロテオミクス解析を行い、シグナル伝達分子群の濃縮、およびTgでの脂質の濃縮が見出された。
3) 超解像度顕微鏡観察で、脂質ラフトを含む部分はZ軸方向のフィロポディア膜と共存し、軸索ガイダンス分子受容体も濃縮することが見出された。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (45 results)

All 2020 2019 2018 Other

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (33 results) (of which Int'l Joint Research: 13 results,  Invited: 10 results) Remarks (1 results)

  • [Journal Article] Microtubule elongation along actin filaments induced by microtubule-associated protein 4 contributes to the formation of cellular protrusions2020

    • Author(s)
      Doki Chihiro、Nishida Kohei、Saito Shoma、Shiga Miyuki、Ogara Hikari、Kuramoto Ayumu、Kuragano Masahiro、Nozumi Motohiro、Igarashi Michihiro、Nakagawa Hiroyuki、Kotani Susumu、Tokuraku Kiyotaka
    • Journal Title

      The Journal of Biochemistry

      Volume: - Issue: 3 Pages: 295-303

    • DOI

      10.1093/jb/mvaa046

    • NAID

      40022375440

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphoproteomic and Bioinformatic Methods for Analyzing Signaling in Vertebrate Axon Growth and Regeneration2020

    • Author(s)
      Igarashi M, Kawasaki A, Ishikawa Y, Honda A, Okada M, Okuda S.
    • Journal Title

      Journal of Neuroscience Methods

      Volume: 339 Pages: 108723-108723

    • DOI

      10.1016/j.jneumeth.2020.108723

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isoform-dependent subcellular localization of LMTK1A and LMTK1B and their roles in axon outgrowth and spine formation2020

    • Author(s)
      Wei Ran、Sugiyama Arika、Sato Yuta、Nozumi Motohiro、Nishino Hironori、Takahashi Miyuki、Saito Taro、Ando Kanae、Fukuda Mitsunori、Tomomura Mineko、Igarashi Michihiro、Hisanaga Shin-ichi
    • Journal Title

      The Journal of Biochemistry

      Volume: - Issue: 1 Pages: 23-32

    • DOI

      10.1093/jb/mvaa019

    • NAID

      40022279141

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular basis of the functions of the mammalian neuronal growth cone revealed using new methods2019

    • Author(s)
      IGARASHI Michihiro
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 95 Issue: 7 Pages: 358-377

    • DOI

      10.2183/pjab.95.026

    • NAID

      130007689028

    • ISSN
      0386-2208, 1349-2896
    • Year and Date
      2019-07-31
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphorylation sites of microtubule-associated protein 1B (MAP1B) involved in axon growth and regeneration2019

    • Author(s)
      Ishikawa Y, Okada M, Honda A, Ito Y, Tamada A, Endo N, Igarashi M
    • Journal Title

      Molecular Brain

      Volume: 12 Issue: 1 Pages: 31711525-31711525

    • DOI

      10.1186/s13041-019-0510-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics2019

    • Author(s)
      Igarashi Michihiro、Okuda Shujiro
    • Journal Title

      Molecular Brain

      Volume: 12 Issue: 1 Pages: 53-53

    • DOI

      10.1186/s13041-019-0476-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration.2019

    • Author(s)
      Adhikara IM, Yagi K, Mayasari DS, Ikeda K, Kitagawa H, Miyata O, Igarashi M, Hatakeyama K, Asada Y, Hirata KI, Emoto N
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 509 Issue: 1 Pages: 89-95

    • DOI

      10.1016/j.bbrc.2018.12.068

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pathological alterations of chondroitin sulfate moiety in postmortem hippocampus of patients with schizophrenia2018

    • Author(s)
      Yukawa、Iwakura、Takei、Saito、Watanabe、Toyooka、Igarashi、Niizato、Oshima、Kunii、Yabe、Matsumoto、Wada、Hino、Iritanii、Niwa、Takeuchi、Takahashi、Kakita、Someya、Nawa
    • Journal Title

      Psychiatry Research

      Volume: 270 Pages: 940-946

    • DOI

      10.1016/j.psychres.2018.10.062

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Craniofacial abnormality with skeletal dysplasia in mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase-12018

    • Author(s)
      Ida-Yonemochi Hiroko、Morita Wataru、Sugiura Nobuo、Kawakami Ryosuke、Morioka Yuki、Takeuchi Yuka、Sato Toshiya、Shibata Shunichi、Watanabe Hideto、Imamura Takeshi、Igarashi Michihiro、Ohshima Hayato、Takeuchi Kosei
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 17134-17134

    • DOI

      10.1038/s41598-018-35412-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] New observations in neuroscience using superresolution microscopy2018

    • Author(s)
      Igarashi Michihiro、Nozumi Motohiro、Wu Ling-Gang、Cella Zanacchi Francesca、Katona Istvan、Barna Laszlo、Xu Pingyong、Zhang Mingshu、Xue Fudong、Boyden Edward
    • Journal Title

      The Journal of Neuroscience

      Volume: 38 Issue: 44 Pages: 9459-9467

    • DOI

      10.1523/jneurosci.1678-18.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Growth cone phosphoproteomics reveals that GAP-43 phosphorylated by JNK is a marker of axon growth and regeneration.2018

    • Author(s)
      Okada M*, Kawasaki A*, Tamada A*, Okuda S, Nozumi M, Ito Y, Kobayashi D, Yamasaki T, Yokoyama R, Shibata T, Nishina H, Yoshida Y, Fujii Y, Takeuchi K, Igarashi M(*These three authorscontributed equally.).
    • Journal Title

      ISCIENCE

      Volume: 4 Pages: 190-203

    • DOI

      10.1016/j.isci.2018.05.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 超解像陰影法(SUSHI)による細胞内構造の可視化2020

    • Author(s)
      野住素広、V. Nagerl、五十嵐道弘
    • Organizer
      生体運動研究合同班会議2020(京都)
    • Related Report
      2019 Annual Research Report
  • [Presentation] JNK dependent phosphorylation sites of GAP-43 is involved in axon growth/regeneration, revealed by growth cone phosphoproteomics2020

    • Author(s)
      A. Kawasaki, A. Tamada, M. Okada, S. Okuda, M. Igarashi
    • Organizer
      AMED-CREST国際シンポジウム(宮崎)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Super-resolution microscopy reveals F-actin-mediated mechanisms of nerve growth and maintenance2020

    • Author(s)
      M. Nozumi,Y. Sato,M. Igarashi
    • Organizer
      AMED-CREST国際シンポジウム(宮崎)
    • Related Report
      2019 Annual Research Report
  • [Presentation] A molecular marker in neural development and plasticity in primates2020

    • Author(s)
      M. Okada, Y. Sato, A. Kawasaki, M. Natsumeda, M. Oishi, K. Sawamoto, Y. Fujii, M. Igarashi
    • Organizer
      AMED-CREST国際シンポジウム(宮崎)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Phosphoproteomics analysis of the growth cone reveals the new molecular markers of growing axons.2019

    • Author(s)
      M. Igarashi
    • Organizer
      7th Mediterranean Neuroscience Conference (Marrakech, Morocco)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新規・小胞体-エンドソーム膜接触部位における脂質交換輸送機構とその生理機能の解明2019

    • Author(s)
      2.河嵜麻実、酒井晶子、荒川聡子、中西正樹、佐々木雄彦、清水重臣、五十嵐道弘、中津史
    • Organizer
      第71回日本生物細胞学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 成長円錐のリン酸化プロテオミクスにより同定されたJNK基質の軸索伸長における役割2019

    • Author(s)
      3.河嵜麻実、高杉俊之、玉田篤史、奥田修二郎、崎村建司、仁科博史、五十嵐道弘
    • Organizer
      第92回日本生化学会大会(横浜)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Lipoquality and development of the GPSN2 knockout mice2019

    • Author(s)
      M. Igarashi, A. Honda, M. Nozumi
    • Organizer
      60th International Conference on the Bioscience of Lipids. (Tokyo)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 成長円錐のリン酸化プロテオミクスにより同定されたGAP-43のJNKリン酸化部位は伸長または再生する神経軸索で活性化される2019

    • Author(s)
      河嵜麻実、玉田篤史、岡田正康、奥田修二郎、仁科博史、山崎世和、五十嵐道弘
    • Organizer
      第42回日本神経科学・第62回日本神経化学合同大会(新潟)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高頻度チロシンリン酸化MAP1Bの神経発生過程における機能解析2019

    • Author(s)
      伊藤泰行、本多敦子、五十嵐道弘
    • Organizer
      第42回日本神経科学・第62回日本神経化学合同大会(新潟)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 発生脳におけるMAP1Bの高頻度リン酸化部位2019

    • Author(s)
      石川裕也、本多敦子、伊藤泰行、河嵜麻実、玉田篤史、遠藤直人、五十嵐道弘
    • Organizer
      第42回日本神経科学・第62回日本神経化学合同大会(新潟)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Evolutional analysis of the protein phosphorylation sites in the growth cone2019

    • Author(s)
      M. Igarashi, S. Okuda
    • Organizer
      ISN (international society for Neurochemistry)-ASN Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高頻度チロシンリン酸化MAP1Bの神経発生過程における機能解析2019

    • Author(s)
      伊藤泰行、本多敦子、五十嵐道弘
    • Organizer
      第92回日本生化学会大会(横浜)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Phosphorylation of MAP1B in the growing/ regrowing axon2019

    • Author(s)
      本多敦子、石川裕也、五十嵐道弘
    • Organizer
      第92回日本生化学会大会(横浜)
    • Related Report
      2019 Annual Research Report
  • [Presentation] The MAP1B phosphorylation sites specifically localized in the developing brain and in the regenerating peripheral nerves2019

    • Author(s)
      Y. Ishikawa, M. Okada, A. Honda, Y. Ito, A. Tamada, N. Endo, M. Igarashi
    • Organizer
      SFN (Society for Neuroscience) annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経成長円錐のタンパク質リン酸化に関する進化のバイオインフォマティクス解析2019

    • Author(s)
      五十嵐道弘、奥田修二郎
    • Organizer
      第42回日本分子生物学会(福岡)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脳発生過程で高頻度にリン酸化されるMAP1Bチロシン残基の同定と機能解析2019

    • Author(s)
      伊藤泰行、本多敦子、五十嵐道弘
    • Organizer
      第42回日本分子生物学会(福岡)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Phosphoproteomic analysis of the mammalian growth cones reveals the novel molecular markers of the growing/regenerating axons, specifically to vertebrate2019

    • Author(s)
      M. Igarashi, Y. Ishikawa, S. Okuda
    • Organizer
      ASCB EMBO 2019 Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コンドロイチン硫酸(CS)合成酵素のノックアウトマウス解析2019

    • Author(s)
      五十嵐 道弘
    • Organizer
      先端動物支援プラットフォーム成果報告会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 3D analysis of the intracellular structures in growth cones using superresolution microscopy2019

    • Author(s)
      M. Igarashi
    • Organizer
      EMBO Molecular Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 哺乳動物成長円錐の分子基盤をどう理解するか?2018

    • Author(s)
      五十嵐 道弘
    • Organizer
      生理学研究所シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] New observations in neuroscience using superresolution microscopy.2018

    • Author(s)
      M. Igarashi
    • Organizer
      Soceity for Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] New relationships between F-actin organization and memberance in the growth cone revealed by SIM2018

    • Author(s)
      M. Nozumi, M. Igarashi
    • Organizer
      Soceity for Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 構造化照明による超解像顕微鏡(SIM)で明らかになった神経突起先端の3次元構造2018

    • Author(s)
      野住 素広、五十嵐 道弘
    • Organizer
      日本分子生物学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 神経細胞の形態形成シグナリングにおけるGPM6aのパルミトイル化と脂質ラフト集積の意義2018

    • Author(s)
      五十嵐 道弘
    • Organizer
      日本神経化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Abnormalities in perineuronal nets (PNN) and behaviors in mice without CSGalNAcT12018

    • Author(s)
      M. Igarashi
    • Organizer
      Glycobiology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Phosphoproteomics of the mammalian growth cone reveals that phosphorylation of GAP-43 by JNK is specific to the growing/regenerating axon2018

    • Author(s)
      M. Igarashi
    • Organizer
      American Society for Cell Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phosphorylation profiles of neuronal growth cones revealed by phosphoproteomics2018

    • Author(s)
      M. Igarashi
    • Organizer
      Gordon Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Growth cone phosphoproteomics reveals that JNK-dependent phosphorylation of GAP-43 is specific to the growing axon2018

    • Author(s)
      A. Kawasaki, M. Igarashi
    • Organizer
      Cold Spring Harbor Asaia Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] JNK-dependent phosphorylation sites of GAP-43 is a marker of axon growth/regeneration, revealed by growth cone phosphoproteomic2018

    • Author(s)
      A. Kawasaki, M.. Igarashi
    • Organizer
      Society for Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 超解像度顕微鏡による成長円錐の3次元細胞内構造解析2018

    • Author(s)
      野住 素広、五十嵐 道弘
    • Organizer
      日本神経科学学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 成長円錐リン酸化プロテオミクスにより神経成長のシグナル伝達2018

    • Author(s)
      河嵜 麻実、五十嵐 道弘
    • Organizer
      日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] イノシトールリン脂質によるメンブレンコンタクト形成と脂質交換輸送制御2018

    • Author(s)
      中津 史
    • Organizer
      日本分子生物学会大会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 新潟大学大学院医歯学総合研究科分子細胞機能学

    • URL

      https://www.med.niigata-u.ac.jp/bc2/

    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2021-01-27  

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