| STON2 variations are involved in synaptic dysfunction and schizophrenia-like behaviors by regulating Syt1 trafficking |
| Ma, YL; Gao, K; Sun, XX; Wang, JX; Yang, Y; Wu, JY; Chai, AP; Yao, L; Liu, N; Yu, H; Su, Y; Lu, TL; Wang, LF; Yue, WH; Zhang, XH; Xu, L ; Zhang, D; Li, J
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| 2024
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| 发表期刊 | SCIENCE BULLETIN
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| ISSN | 2095-9273
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| 卷号 | 69期号:10页码:1458-1471 |
| 摘要 | Synaptic dysfunction is a core component of the pathophysiology of schizophrenia. However, the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood. The Stonin 2 (STON2) gene encodes a major adaptor for clathrin-mediated endocytosis (CME) of synaptic vesicles. In this study, we showed that the C-C (307Pro-851Ala) haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia -like behaviors through the regulation of CME. We found that schizophrenia -related STON2 variations led to protein dephosphorylation, which affected its interaction with synaptotagmin 1 (Syt1), a calcium sensor protein located in the presynaptic membrane that is critical for CME. STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission, short-term plasticity, and schizophrenia -like behaviors. Moreover, among seven antipsychotic drugs, patients with the C -C (307Pro-851Ala) haplotype responded better to haloperidol than did the T -A (307Ser-851Ser) carriers. The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia -like behaviors in STON2307Pro851Ala knockin mice. Our findings demonstrated the effect of schizophreniarelated STON2 variations on synaptic dysfunction through the regulation of CME, which might be attractive therapeutic targets for treating schizophrenia -like phenotypes. (c) 2024 Science China Press. Published by Elsevier B.V. and Science China Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| 收录类别 | sci
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/14245
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| 专题 | 科研部门_学习记忆的分子神经机制（徐林）
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推荐引用方式
GB/T 7714 |
Ma, YL,Gao, K,Sun, XX,et al. STON2 variations are involved in synaptic dysfunction and schizophrenia-like behaviors by regulating Syt1 trafficking[J]. SCIENCE BULLETIN,2024,69(10):1458-1471.
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| APA |
Ma, YL.,Gao, K.,Sun, XX.,Wang, JX.,Yang, Y.,...&Li, J.(2024).STON2 variations are involved in synaptic dysfunction and schizophrenia-like behaviors by regulating Syt1 trafficking.SCIENCE BULLETIN,69(10),1458-1471.
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| MLA |
Ma, YL,et al."STON2 variations are involved in synaptic dysfunction and schizophrenia-like behaviors by regulating Syt1 trafficking".SCIENCE BULLETIN 69.10(2024):1458-1471.
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