Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33758193.
- Also identified by DOI 10.1038/s41467-021-22059-6 and PMC identifier 7988105.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Autism Spectrum Disorder
- Calcium-Binding Proteins
- Cell Adhesion Molecules, Neuronal
- Membrane Proteins
- Nerve Tissue Proteins
- Neural Cell Adhesion Molecules
- Neurons
- Receptor-Like Protein Tyrosine Phosphatases, Class 2