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祖先型ニューレキシンの構造・機能解析

Research Project

Project/Area Number 19J20655
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionOkinawa Institute of Science and Technology Graduate University

Principal Investigator

Guzman Christine  沖縄科学技術大学院大学, 科学技術研究科, 特別研究員(DC1)

Project Period (FY) 2019-04-25 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2021: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2020: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2019: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsNematostella / neurexins / synaptic protein / Cnidaria / basal Metazoa / synapse / Neurexin / evolution / basal animals / protein interaction
Outline of Research at the Start

This study attempts to reconstruct the structure and determine the core function of ancestral Neurexins using basal animals. Phylum-wide survey of Nrxn genes will be performed to obtain detailed insights into the evolutionary processes of synaptic structural protein complexes. Mass Spectrometry (XL-MS) will be conducted to identify binding partners of endogenous Nrxn proteins in non-neural Trichoplax and neuron/synapse-bearing basal metazoans (Nematostella, Bolinopsis). Synaptic and/or non-synaptic functions of ancestral Nrxns will be examined using various functional assays.

Outline of Annual Research Achievements

This project elucidated the role of Neurexins (Nrxns) in the early evolution of the nervous system. Nrxns are core presynaptic cell adhesion molecules with critical functions in the chemical synapse, but their origin and evolutionary history remain underexplored. I employed a multidisciplinary approach to give the first characterization of Nrxn-mediated neuronal signaling outside Bilateria. I showed that in Nematostella vectensis, a member of Cnidaria which is the closest outgroup to Bilateria, knocking down the neuronally expressed Nrxns resulted in abnormal behaviors involving muscle contraction. I demonstrated that the neural Nrxns in N. vectensis are required for the transmission of classical chemical transmitters (e.g., glutamate, glycine) but not for neuropeptide signaling.
Additionally, a non-neural function of N. vectensis Nrxns was that may explain how and why this family of proteins was employed in the synaptic machinery of the early nervous system. Functional analysis of the broadly expressed Nrxns in N. vectensis revealed their major role in heterologous cell-cell adhesion; in particular, in the maintenance of the junction between ectodermal and endodermal epithelial cells.
I have completed all the experiments by the end of FY2021. In FY2022 (April to October), I performed additional experiments for the manuscript that is being prepared for submission.

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (4 results)

All 2022 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Mass spectrometry of short peptides reveals common features of metazoan peptidergic neurons2022

    • Author(s)
      Hayakawa Eisuke、Guzman Christine、Horiguchi Osamu、Kawano Chihiro、Shiraishi Akira、Mohri Kurato、Lin Mei-Fang、Nakamura Ryotaro、Nakamura Ryo、Kawai Erina、Komoto Shinya、Jokura Kei、Shiba Kogiku、Shigenobu Shuji、Satake Honoo、Inaba Kazuo、Watanabe Hiroshi
    • Journal Title

      Nature Ecology and Evolution

      Volume: 6 Issue: 10 Pages: 1438-1448

    • DOI

      10.1038/s41559-022-01835-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Mass spectrometry of short peptides reveals common features of metazoan peptidergic neurons2022

    • Author(s)
      Christine Guzman
    • Organizer
      The 45th Annual Meeting of the Molecular Biology Society of Japan (MBSJ2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] From Diffusion to Network: A Neurexin View of the Origin of Neural Synapse2019

    • Author(s)
      Christine Guzman
    • Organizer
      OIST Marine Science Day (OIST Graduate University)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Functional and Structural Analyses of Neurexin-Mediated Synaptic Complexes in Early-Branching Animals2019

    • Author(s)
      Christine Guzman
    • Organizer
      The Identity and Evolution of Cell Types (EMBL Heidelberg)
    • Related Report
      2019 Annual Research Report

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Published: 2019-05-29   Modified: 2024-03-26  

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