Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice
説明
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.
収録刊行物
-
- Nature Communications
-
Nature Communications 12 1848-, 2021-03-23
Springer Nature
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1050287525747819648
-
- NII論文ID
- 120006996978
-
- ISSN
- 20411723
-
- HANDLE
- 2433/262408
-
- PubMed
- 33758193
-
- 本文言語コード
- en
-
- 資料種別
- journal article
-
- データソース種別
-
- IRDB
- Crossref
- CiNii Articles
- KAKEN
- OpenAIRE