1. Cell Biology
  2. Neuroscience
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Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory

  1. Junjun Zhao
  2. Albert Hiu Ka Fok
  3. Ruolin Fan
  4. Pui-Yi Kwan
  5. Hei-Lok Chan
  6. Louisa Hoi-Ying Lo
  7. Ying-Shing Chan
  8. Wing-Ho Yung
  9. Jiandong Huang
  10. Cora Sau Wan Lai  Is a corresponding author
  11. Kwok-On Lai  Is a corresponding author
  1. University of Hong Kong, Hong Kong
  2. Chinese University of Hong Kong, Hong Kong
Research Article
  • Cited 16
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Cite this article as: eLife 2020;9:e53456 doi: 10.7554/eLife.53456

Abstract

The kinesin I family of motor proteins are crucial for axonal transport, but their roles in dendritic transport and postsynaptic function are not well-defined. Gene duplication and subsequent diversification give rise to three homologous kinesin I proteins (KIF5A, KIF5B and KIF5C) in vertebrates, but it is not clear whether and how they exhibit functional specificity. Here we show that knockdown of KIF5A or KIF5B differentially affects excitatory synapses and dendritic transport in hippocampal neurons. The functional specificities of the two kinesins are determined by their diverse carboxyl-termini, where arginine methylation occurs in KIF5B and regulates its function. KIF5B conditional knockout mice exhibit deficits in dendritic spine morphogenesis, synaptic plasticity and memory formation. Our findings provide insights into how expansion of the kinesin I family during evolution leads to diversification and specialization of motor proteins in regulating postsynaptic function.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Junjun Zhao

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  2. Albert Hiu Ka Fok

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  3. Ruolin Fan

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  4. Pui-Yi Kwan

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5402-9122
  5. Hei-Lok Chan

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  6. Louisa Hoi-Ying Lo

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  7. Ying-Shing Chan

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  8. Wing-Ho Yung

    School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  9. Jiandong Huang

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  10. Cora Sau Wan Lai

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    For correspondence
    coraswl@hku.hk
    Competing interests
    The authors declare that no competing interests exist.
  11. Kwok-On Lai

    School of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong Kong
    For correspondence
    laiko@hku.hk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4069-054X

Funding

Research Grant Council of Hong Kong (GRF 16100814)

  • Kwok-On Lai

Shenzhen Peacock Team Project (KQTD2015033117210153)

  • Jiandong Huang

Shenzhen Science Technology Innovation Committee Basic Science Research Grant (JCYJ20170413154523577)

  • Jiandong Huang

University Grants Committee of Hong Kong (AoE/M-604/16)

  • Wing-Ho Yung

University Grants Committee of Hong Kong (T13-605/18-W)

  • Kwok-On Lai

Research Grant Council of Hong Kong (GRF 17135816)

  • Kwok-On Lai

Research Grant Council of Hong Kong (GRF 17106018)

  • Kwok-On Lai

Research Grant Council of Hong Kong (ECS 27119715)

  • Kwok-On Lai

University Grants Committee of Hong Kong (AoE/M-604/16)

  • Kwok-On Lai

Research Grant Council of Hong Kong (ECS 27103715)

  • Cora Sau Wan Lai

Research Grant Council of Hong Kong (GRF 17128816)

  • Cora Sau Wan Lai

National Natural Science Foundation of China (NSFC/General Program 31571031)

  • Cora Sau Wan Lai

Health and Medical Research Fund Hong Kong (03143096)

  • Cora Sau Wan Lai

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 approved and performed in accordance with University of Hong Kong Committee on the Use of Live Animals (CULATR 3935-16 and CULATR 4056-16) and in Teaching and Research guidelines.

Reviewing Editor

  1. Eunjoon Kim, Institute for Basic Science, Korea Advanced Institute of Science and Technology, Republic of Korea

Publication history

  1. Received: November 8, 2019
  2. Accepted: January 20, 2020
  3. Accepted Manuscript published: January 21, 2020 (version 1)
  4. Version of Record published: February 18, 2020 (version 2)

Copyright

© 2020, Zhao 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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