| First Author | Um SM | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 13 | Pages | 3839-3851 |
| PubMed ID | 29949768 | Mgi Jnum | J:270409 |
| Mgi Id | MGI:6278330 | Doi | 10.1016/j.celrep.2018.05.087 |
| Citation | Um SM, et al. (2018) NGL-2 Deletion Leads to Autistic-like Behaviors Responsive to NMDAR Modulation. Cell Rep 23(13):3839-3851 |
| abstractText | Netrin-G ligand 2 (NGL-2)/LRRC4, implicated in autism spectrum disorders and schizophrenia, is a leucine-rich repeat-containing postsynaptic adhesion molecule that interacts intracellularly with the excitatory postsynaptic scaffolding protein PSD-95 and trans-synaptically with the presynaptic adhesion molecule netrin-G2. Functionally, NGL-2 regulates excitatory synapse development and synaptic transmission. However, whether it regulates synaptic plasticity and disease-related specific behaviors is not known. Here, we report that mice lacking NGL-2 (Lrrc4(-/-) mice) show suppressed N-Methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the hippocampus. NGL-2 associates with NMDARs through both PSD-95-dependent and -independent mechanisms. Moreover, Lrrc4(-/-) mice display mild social interaction deficits and repetitive behaviors that are rapidly improved by pharmacological NMDAR activation. These results suggest that NGL-2 promotes synaptic stabilization of NMDARs, regulates NMDAR-dependent synaptic plasticity, and prevents autistic-like behaviors from developing in mice, supporting the hypothesis that NMDAR dysfunction contributes to autism spectrum disorders. |
