| First Author | Yoshida T | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 1848 |
| PubMed ID | 33758193 | Mgi Jnum | J:303834 |
| Mgi Id | MGI:6515256 | Doi | 10.1038/s41467-021-22059-6 |
| Citation | Yoshida T, et al. (2021) Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice. Nat Commun 12(1):1848 |
| abstractText | 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 delta (PTPdelta) splice variants, competing with NRXN binding. NLGN3-PTPdelta complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPdelta and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPdelta 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. |
