1. Neuroscience
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Presynaptic PTPσ regulates postsynaptic NMDA receptor function through direct adhesion-independent mechanisms

  1. Kyungdeok Kim
  2. Wangyong Shin
  3. Muwon Kang
  4. Suho Lee
  5. Doyoun Kim
  6. Ryeonghwa Kang
  7. Yewon Jung
  8. Yisul Cho
  9. Esther Yang
  10. Hyun Kim
  11. Yong Chul Bae
  12. Eunjoon Kim  Is a corresponding author
  1. Korea Advanced Institute of Science and Technology, Republic of Korea
  2. Institute for Basic Science, Republic of Korea
  3. Kyungpook National University, Republic of Korea
  4. Korea University, Republic of Korea
  5. Institute for Basic Science, Korea Advanced Institute of Science and Technology, Republic of Korea
Research Article
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Cite this article as: eLife 2020;9:e54224 doi: 10.7554/eLife.54224

Abstract

Synaptic adhesion molecules regulate synapse development and function. However, whether and how presynaptic adhesion molecules regulate postsynaptic NMDAR function remains largely unclear. Presynaptic LAR family receptor tyrosine phosphatases (LAR-RPTPs) regulate synapse development through mechanisms that include trans-synaptic adhesion; however, whether they regulate postsynaptic receptor functions remains unknown. Here we report that presynaptic PTPσ, a LAR-RPTP, enhances postsynaptic NMDA receptor (NMDAR) currents and NMDAR-dependent synaptic plasticity in the hippocampus. This regulation does not involve trans-synaptic adhesions of PTPσ, suggesting that the cytoplasmic domains of PTPσ, known to have tyrosine phosphatase activity and mediate protein-protein interactions, are important. In line with this, phosphotyrosine levels of presynaptic proteins, including neurexin-1, are strongly increased in PTPσ-mutant mice. Behaviorally, PTPσ-dependent NMDAR regulation is important for social and reward-related novelty recognition. These results suggest that presynaptic PTPσ regulates postsynaptic NMDAR function through trans-synaptic and direct adhesion-independent mechanisms and novelty recognition in social and reward contexts.

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. Kyungdeok Kim

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  2. Wangyong Shin

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  3. Muwon Kang

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  4. Suho Lee

    Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  5. Doyoun Kim

    Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  6. Ryeonghwa Kang

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  7. Yewon Jung

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    Competing interests
    No competing interests declared.
  8. Yisul Cho

    Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea
    Competing interests
    No competing interests declared.
  9. Esther Yang

    Department of Anatomy, Korea University, Seoul, Republic of Korea
    Competing interests
    No competing interests declared.
  10. Hyun Kim

    Department of Anatomy and Division of Brain Korea, Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
    Competing interests
    No competing interests declared.
  11. Yong Chul Bae

    Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea
    Competing interests
    No competing interests declared.
  12. Eunjoon Kim

    Center for Synaptic Brain Dysfunctions, Department of Biological Sciences, Institute for Basic Science, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    For correspondence
    kime@kaist.ac.kr
    Competing interests
    Eunjoon Kim, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5518-6584

Funding

Institute for Basic Science (IBS-R002-D1)

  • Eunjoon Kim

The National Research Foundation of Korea (MSIT,NRF-2017R1A5A2015391)

  • Yong Chul Bae

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 mice were housed and bred at the mouse facility of Korea Advanced Institute of Science and Technology (KAIST) and maintained according to the Animal Research Requirements of KAIST. All procedures were approved by the Committee of Animal Research at KAIST (KA2016-33)

Reviewing Editor

  1. Gary L Westbrook, Oregon Health and Science University, United States

Publication history

  1. Received: December 6, 2019
  2. Accepted: March 4, 2020
  3. Accepted Manuscript published: March 6, 2020 (version 1)
  4. Version of Record published: March 13, 2020 (version 2)

Copyright

© 2020, Kim 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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