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
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