Rare NRXN1 missense variants identified in autism interfered protein degradation and Drosophila sleeping
| Autor: | Lu Xia, Yalan Liu, Yaowen Zhang, Rongjuan Zhao, Yu Peng, Taoxi Li, Cenying Liu, Lu Shen, Jingjing Chen, Sanchuan Luo, Kun Xia |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Genetics
Autism Spectrum Disorder Calcium-Binding Proteins Mutation Missense Synaptogenesis Protein degradation Biology medicine.disease Phenotype In vitro Pathogenesis Psychiatry and Mental health Proteolysis medicine Animals Humans Autism Missense mutation Drosophila Autistic Disorder Sleep Neural Cell Adhesion Molecules Biological Psychiatry Function (biology) |
| Zdroj: | Journal of Psychiatric Research. 143:113-122 |
| ISSN: | 0022-3956 |
| Popis: | NRXN1 is involved in synaptogenesis and have been implicated in Autism spectrum disorders. However, many rare inherited missense variants of NRXN1 have not been thoroughly evaluated. Here, functional analyses in vitro and in Drosophila of three NRXN1 missense mutations, Y282H, L893V, and I1135V identified in ASD patients in our previous study were performed. Our results showed these three mutations interfered protein degradation compared with NRXN1-WT protein. Expressing human NRXN1 in Drosophila could lead to abnormal circadian rhythm and sleep behavior, and three mutated proteins caused milder phenotypes, indicating the mutations may change the function of NRXN1 slightly. These findings highlight the functional role of rare NRXN1 missense variants identified in autism patients, and provide clues for us to better understand the pathogenesis of abnormal circadian rhythm and sleep behavior of other organisms, including humans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect