Functional significance of rare neuroligin 1 variants found in autism

• DOI: 10.1371/journal.pgen.1006940
• Publication Date: 2017-08-25T17:33:43Z
• Authors: Moe Nakanishi; Jun Nomura; Xiao Ji; Kota Tamada; Takashi Arai; Eiki Takahashi; Maja Bućan; Toru Takumi
• Keywords: Neuroligin; Neurodevelopmental disorder; Heritability of autism

Genetic mutations contribute to the etiology of autism spectrum disorder (ASD), a common, heterogeneous neurodevelopmental characterized by impairments in social interaction, communication, and repetitive restricted patterns behavior. Since neuroligin3 (NLGN3), cell adhesion molecule at neuronal synapse, was first identified as risk gene for ASD, several additional variants NLGN3 NLGN4 were found ASD patients. Moreover, synaptopathies are now known cause neuropsychiatric disorders including ASD. In humans, NLGNs consist five family members, neuroligin1 (NLGN1) is major component forming complex on excitatory glutamatergic synapses. However, significance NLGN1 remains unknown. Here, we systematically examine missense that detected patients, show molecular cellular alterations caused these variants. We novel Pro89Leu (P89L) variant two siblings leads changes localization, protein degradation, impairment spine formation. Furthermore, generated knock-in P89L mice, heterozygote mice display abnormal behavior, core feature These results, time, implicate rare functionally significant support NLGN synaptic pathway importance disorders.