1. Cell Biology
  2. Neuroscience

Microtubule assembly by soluble tau impairs vesicle endocytosis and excitatory neurotransmission via dynamin sequestration in Alzheimer's disease mice synapse model

  1. Tetsuya Hori
  2. Kohgaku Eguchi
  3. Han-Ying Wang
  4. Tomohiro Miyasaka
  5. Laurent Guillaud
  6. Zacharie Taoufiq
  7. Satyajit Mahapatra
  8. Hiroshi Yamada
  9. Kohji Takei
  10. Tomoyuki Takahashi  Is a corresponding author
  1. Okinawa Institute of Science and Technology - Graduate University, Japan
  2. Institute of Science and Technology Austria, Austria
  3. Doshisha University, Japan
  4. Okayama University, Japan
https://doi.org/10.7554/eLife.73542
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Cite this article
  1. Tetsuya Hori
  2. Kohgaku Eguchi
  3. Han-Ying Wang
  4. Tomohiro Miyasaka
  5. Laurent Guillaud
  6. Zacharie Taoufiq
  7. Satyajit Mahapatra
  8. Hiroshi Yamada
  9. Kohji Takei
  10. Tomoyuki Takahashi
(2022)
Microtubule assembly by soluble tau impairs vesicle endocytosis and excitatory neurotransmission via dynamin sequestration in Alzheimer's disease mice synapse model
eLife 11:e73542.
https://doi.org/10.7554/eLife.73542
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Abstract

Elevation of soluble wild-type (WT) tau occurs in synaptic compartments in Alzheimer's disease. We addressed whether tau elevation affects synaptic transmission at the calyx of Held in slices from mice brainstem. Whole-cell loading of WT human tau (h-tau) in presynaptic terminals at 10-20 µM caused microtubule (MT) assembly and activity-dependent rundown of excitatory neurotransmission. Capacitance measurements revealed that the primary target of WT h-tau is vesicle endocytosis. Blocking MT assembly using nocodazole prevented tau-induced impairments of endocytosis and neurotransmission. Immunofluorescence imaging analyses revealed that MT assembly by WT h-tau loading was associated with an increased MT-bound fraction of the endocytic protein dynamin. A synthetic dodecapeptide corresponding to dynamin-1-pleckstrin-homology domain inhibited MT-dynamin interaction and rescued tau-induced impairments of endocytosis and neurotransmission. We conclude that elevation of presynaptic WT tau induces de novo assembly of MTs, thereby sequestering free dynamins. As a result, endocytosis and subsequent vesicle replenishment are impaired, causing activity-dependent rundown of neurotransmission.

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All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for All Figures.

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Author details

  1. Tetsuya Hori

    Cellular and Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology - Graduate University, Okinawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0823-3306

  2. Kohgaku Eguchi

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6170-2546

  3. Han-Ying Wang

    Cellular and Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology - Graduate University, Okinawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3021-7134

  4. Tomohiro Miyasaka

    Faculty of Life and Medical Sciences, Doshisha University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.

  5. Laurent Guillaud

    Cellular and Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology - Graduate University, Okinawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9688-0991

  6. Zacharie Taoufiq

    Cellular and Molecular Synaptic Function Unit,, Okinawa Institute of Science and Technology - Graduate University, Okinawa, Japan
    Competing interests
    The authors declare that no competing interests exist.

  7. Satyajit Mahapatra

    Cellular and Molecular Synaptic Function Unit,, Okinawa Institute of Science and Technology - Graduate University, Okinawa, Japan
    Competing interests
    The authors declare that no competing interests exist.

  8. Hiroshi Yamada

    Department of Neuroscience, Okayama University, Okayama, Japan
    Competing interests
    The authors declare that no competing interests exist.

  9. Kohji Takei

    Department of Neuroscience, Okayama University, Okayama, Japan
    Competing interests
    The authors declare that no competing interests exist.

  10. Tomoyuki Takahashi

    Cellular and Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology - Graduate University, Okinawa, Japan
    For correspondence
    ttakahas@oist.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8771-7666

Funding

Okinawa Institute of Science and Technology Graduate University

  • Tomoyuki Takahashi

Core Research for Evolutional Science and Technology

  • Tomoyuki Takahashi

Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research on Innovative Areas,26117004)

  • Tomohiro Miyasaka

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed in accordance with the guidelines of the Physiological Society of Japan and animal experiment regulations at Okinawa Institute of Science and Technology Graduate University.

Copyright

© 2022, Hori et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Tetsuya Hori
  2. Kohgaku Eguchi
  3. Han-Ying Wang
  4. Tomohiro Miyasaka
  5. Laurent Guillaud
  6. Zacharie Taoufiq
  7. Satyajit Mahapatra
  8. Hiroshi Yamada
  9. Kohji Takei
  10. Tomoyuki Takahashi
(2022)
Microtubule assembly by soluble tau impairs vesicle endocytosis and excitatory neurotransmission via dynamin sequestration in Alzheimer's disease mice synapse model
eLife 11:e73542.
https://doi.org/10.7554/eLife.73542

Share this article

https://doi.org/10.7554/eLife.73542

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