IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-22059-6.html
   My bibliography  Save this article

Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice

Author

Listed:
  • Tomoyuki Yoshida

    (University of Toyama
    University of Toyama
    JST PRESTO)

  • Atsushi Yamagata

    (RIKEN Center for Biosystems Dynamics Research)

  • Ayako Imai

    (University of Toyama)

  • Juhyon Kim

    (University of Toyama)

  • Hironori Izumi

    (University of Toyama)

  • Shogo Nakashima

    (University of Toyama)

  • Tomoko Shiroshima

    (Kitasato University School of Medicine)

  • Asami Maeda

    (Juntendo University Graduate School of Medicine)

  • Shiho Iwasawa-Okamoto

    (University of Toyama)

  • Kenji Azechi

    (University of Toyama)

  • Fumina Osaka

    (Hokkaido University)

  • Takashi Saitoh

    (Hokkaido University)

  • Katsumi Maenaka

    (Hokkaido University
    Hokkaido University)

  • Takashi Shimada

    (SHIMADZU Bioscience Research Partnership, Innovation Center, Shimadzu Scientific Instruments)

  • Yuko Fukata

    (National Institutes of Natural Sciences)

  • Masaki Fukata

    (National Institutes of Natural Sciences)

  • Jumpei Matsumoto

    (University of Toyama
    University of Toyama)

  • Hisao Nishijo

    (University of Toyama
    University of Toyama)

  • Keizo Takao

    (University of Toyama
    University of Toyama)

  • Shinji Tanaka

    (The University of Tokyo)

  • Shigeo Okabe

    (The University of Tokyo)

  • Katsuhiko Tabuchi

    (JST PRESTO
    Shinshu University
    Shinshu University)

  • Takeshi Uemura

    (Shinshu University
    Shinshu University)

  • Masayoshi Mishina

    (Ritsumeikan University)

  • Hisashi Mori

    (University of Toyama
    University of Toyama)

  • Shuya Fukai

    (Kyoto University)

Abstract

Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase δ (PTPδ) splice variants, competing with NRXN binding. NLGN3-PTPδ complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPδ and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPδ interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality.

Suggested Citation

  • Tomoyuki Yoshida & Atsushi Yamagata & Ayako Imai & Juhyon Kim & Hironori Izumi & Shogo Nakashima & Tomoko Shiroshima & Asami Maeda & Shiho Iwasawa-Okamoto & Kenji Azechi & Fumina Osaka & Takashi Saito, 2021. "Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22059-6
    DOI: 10.1038/s41467-021-22059-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-22059-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-22059-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Alessandra Sclip & Thomas C. Südhof, 2023. "Combinatorial expression of neurexins and LAR-type phosphotyrosine phosphatase receptors instructs assembly of a cerebellar circuit," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22059-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.