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ATP-dependent coupling of pre- and post-synaptic organelles movements at central synapses and its implication in synaptic plasticity and transmission

Research Project

Project/Area Number 18K06494
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionOkinawa Institute of Science and Technology Graduate University

Principal Investigator

Guillaud Laurent  沖縄科学技術大学院大学, 細胞分子シナプス機能ユニット, 研究員 (90596222)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Granted (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsLiquid phase separation / Synapse / Mitochondria / ATP / Neurodegeneration / synaptic vesicle / active zone / cytosol / solubility / Neuroscience / Trafficking / Imaging
Outline of Annual Research Achievements

For the third year my research project has progressed according to plan but with a slight delay due to my move to a new research unit. However this move allowed me to also expand my work to motor neurons and related neurodegenerative pathologies.
1) I have now completed the in vitro analysis of 6 proteins involved in Parkinson and Alzheimer diseases and quantified the number and size of their condensates at 37C and in the presence or absence of ATP. I also determined the threshold concentration of ATP required to prevent liquid phase separation of each of these proteins. 2) I have also performed liquid phase separation in vitro assay on 2 additional proteins implicated in ALS disease, and demonstrated that they also undergo ATP-dependent condensation/decondensation at 37C. 3) I have also performed preliminary experiments on cultured motor neurons (derived from human iPSC and/or mouse ES cells) and show that cytosolic GFP liquid phase separation follow the same mitochondria/ATP-dependent mechanism as I previously reported in giant glutamatergic terminals, suggesting a common and conserve LPS regulation mechanism among different neuronal populations. 4) Additionally I also analyzed LPS in cultured human glutamatergic neurons (derived from iPSCs) using FRAP, as well as quantified and compared ATP concentration in normal and Alzheimer cultured neurons by in vitro luminescence assay. 5) I have written and prepared the initial draft of the manuscript

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

As I moved to a different unit at the end of 2019, my work has been slightly delayed. In addition I have also started to collect new data on different type of neurons (derived from human iPSCs or mouse ESCs) as well as on several proteins involved in ALS disease.

Strategy for Future Research Activity

My next research plan is to increase the number of data on motor neurons cytosolic phase separation and in vitro data on additional proteins involved in ALS or SMA.
Lastly I am planning to submit the manuscript in the first half of 2021.

Report

(3 results)
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report

Research Products

(7 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Anterograde Axonal Transport in Neuronal Homeostasis and Disease2020

    • Author(s)
      Guillaud Laurent、El-Agamy Sara Emad、Otsuki Miki、Terenzio Marco
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 13

    • DOI

      10.3389/fnmol.2020.556175

    • Related Report
      2020 Research-status Report
  • [Journal Article] Spatiotemporally tracking of nano-biofilaments inside the nuclear pore complex core2020

    • Author(s)
      Mohamed Mahmoud Shaaban、Hazawa Masaharu、Kobayashi Akiko、Guillaud Laurent、Watanabe-Nakayama Takahiro、Nakayama Mizuho、Wang Hanbo、Kodera Noriyuki、Oshima Masanobu、Ando Toshio、Wong Richard W.
    • Journal Title

      Biomaterials

      Volume: 256 Pages: 120198-120198

    • DOI

      10.1016/j.biomaterials.2020.120198

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microtubule and Actin Differentially Regulate Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission2019

    • Author(s)
      Piriya Ananda Babu Lashmi、Wang Han-Ying、Eguchi Kohgaku、Guillaud Laurent、Takahashi Tomoyuki
    • Journal Title

      The Journal of Neuroscience

      Volume: 40 Pages: 131-142

    • DOI

      10.1523/jneurosci.1571-19.2019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Culture of mouse giant central nervous system synapses and application for imaging and electrophysiological analyses2018

    • Author(s)
      Dimitar Dimitrov, Laurent Guillaud, Kohgaku Eguchi and Tomoyuki Takahashi
    • Journal Title

      Methods in Molecular Biology

      Volume: 1727 Pages: 201-215

    • DOI

      10.1007/978-1-4939-7571-6_15

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ATP-dependent liquid phase transitions in synapse organization and neurodegeneration2020

    • Author(s)
      Laurent Guillaud
    • Organizer
      2nd Osaka University/OIST Symposium
    • Related Report
      2019 Research-status Report
  • [Presentation] Mitochondrial activity-dependent phase changes of pre-synaptic bio-condensates regulate synchronous trafficking of synaptic vesicles and AMPA receptors in giant mammalian synapses2018

    • Author(s)
      Laurent Guillaud and Tomoyuki Takahashi
    • Organizer
      Gordon Research Conference "Cell Biology of neuron"
    • Related Report
      2018 Research-status Report
  • [Presentation] ATP-dependent phase transitions of peri-active zone and active zone bio-condensates regulate synapse organization and function2018

    • Author(s)
      Laurent Guillaud
    • Organizer
      ASCB/EMBO 2018 Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2021-12-27  

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