The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling
Summary: Previous genetic and biological evidence converge on the involvement of synaptic dysfunction in schizophrenia, and OPCML, encoding a synaptic membrane protein, is reported to be genetically associated with schizophrenia. However, its role in the pathophysiology of schizophrenia remains larg...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719311532 |
| _version_ | 1819049188000792576 |
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| author | Zhengrong Zhang Maoqing Ye Qiongwei Li Yang You Hao Yu Yuanlin Ma Liwei Mei Xiaqin Sun Lifang Wang Weihua Yue Rena Li Jun Li Dai Zhang |
| author_facet | Zhengrong Zhang Maoqing Ye Qiongwei Li Yang You Hao Yu Yuanlin Ma Liwei Mei Xiaqin Sun Lifang Wang Weihua Yue Rena Li Jun Li Dai Zhang |
| author_sort | Zhengrong Zhang |
| collection | DOAJ |
| description | Summary: Previous genetic and biological evidence converge on the involvement of synaptic dysfunction in schizophrenia, and OPCML, encoding a synaptic membrane protein, is reported to be genetically associated with schizophrenia. However, its role in the pathophysiology of schizophrenia remains largely unknown. Here, we found that Opcml is strongly expressed in the mouse hippocampus; ablation of Opcml leads to reduced phosphorylated cofilin and dysregulated F-actin dynamics, which disturbs the spine maturation. Furthermore, Opcml interacts with EphB2 to control the stability of spines by regulating the ephrin-EphB2-cofilin signaling pathway. Opcml-deficient mice display impaired cognitive behaviors and abnormal sensorimotor gating, which are similar to features in neuropsychiatric disorders such as schizophrenia. Notably, the administration of aripiprazole partially restores the abnormal behaviors in Opcml−/− mice by increasing the phosphorylated cofilin level and facilitating spine maturation. We demonstrated a critical role of the schizophrenia-susceptible gene OPCML in spine maturation and cognitive behaviors via regulating the ephrin-EphB2-cofilin signaling pathway, providing further insights into the characteristics of schizophrenia. : Zhang et al. investigate the mechanism of the schizophrenia-associated opioid-binding protein/cell adhesion molecule (OPCML) in spine maturation and its role in general cognitive function using an Opcml-deficient mouse model. Opcml mediates postsynaptic ephrin-EphB2-cofilin signaling in the regulation of spine maturation, which is involved in the pathogenic mechanism of neurodevelopmental disorders such as schizophrenia. Keywords: schizophrenia, OPCML, spine maturation, cofilin, EphB2 signaling, aripiprazole, cognition |
| first_indexed | 2024-12-21T11:28:10Z |
| format | Article |
| id | doaj.art-34ae3a3a169e461db7b871333ed27614 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T11:28:10Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-34ae3a3a169e461db7b871333ed276142022-12-21T19:05:37ZengElsevierCell Reports2211-12472019-10-012914961.e7The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin SignalingZhengrong Zhang0Maoqing Ye1Qiongwei Li2Yang You3Hao Yu4Yuanlin Ma5Liwei Mei6Xiaqin Sun7Lifang Wang8Weihua Yue9Rena Li10Jun Li11Dai Zhang12Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, ChinaNational Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; Corresponding authorPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; Corresponding authorSummary: Previous genetic and biological evidence converge on the involvement of synaptic dysfunction in schizophrenia, and OPCML, encoding a synaptic membrane protein, is reported to be genetically associated with schizophrenia. However, its role in the pathophysiology of schizophrenia remains largely unknown. Here, we found that Opcml is strongly expressed in the mouse hippocampus; ablation of Opcml leads to reduced phosphorylated cofilin and dysregulated F-actin dynamics, which disturbs the spine maturation. Furthermore, Opcml interacts with EphB2 to control the stability of spines by regulating the ephrin-EphB2-cofilin signaling pathway. Opcml-deficient mice display impaired cognitive behaviors and abnormal sensorimotor gating, which are similar to features in neuropsychiatric disorders such as schizophrenia. Notably, the administration of aripiprazole partially restores the abnormal behaviors in Opcml−/− mice by increasing the phosphorylated cofilin level and facilitating spine maturation. We demonstrated a critical role of the schizophrenia-susceptible gene OPCML in spine maturation and cognitive behaviors via regulating the ephrin-EphB2-cofilin signaling pathway, providing further insights into the characteristics of schizophrenia. : Zhang et al. investigate the mechanism of the schizophrenia-associated opioid-binding protein/cell adhesion molecule (OPCML) in spine maturation and its role in general cognitive function using an Opcml-deficient mouse model. Opcml mediates postsynaptic ephrin-EphB2-cofilin signaling in the regulation of spine maturation, which is involved in the pathogenic mechanism of neurodevelopmental disorders such as schizophrenia. Keywords: schizophrenia, OPCML, spine maturation, cofilin, EphB2 signaling, aripiprazole, cognitionhttp://www.sciencedirect.com/science/article/pii/S2211124719311532 |
| spellingShingle | Zhengrong Zhang Maoqing Ye Qiongwei Li Yang You Hao Yu Yuanlin Ma Liwei Mei Xiaqin Sun Lifang Wang Weihua Yue Rena Li Jun Li Dai Zhang The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling Cell Reports |
| title | The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling |
| title_full | The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling |
| title_fullStr | The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling |
| title_full_unstemmed | The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling |
| title_short | The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling |
| title_sort | schizophrenia susceptibility gene opcml regulates spine maturation and cognitive behaviors through eph cofilin signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719311532 |
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