Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke
Summary: Synaptotagmin III (Syt3) is a Ca2+-dependent membrane-traffic protein that is highly concentrated in synaptic plasma membranes and affects synaptic plasticity by regulating post-synaptic receptor endocytosis. Here, we show that Syt3 is upregulated in the penumbra after ischemia/reperfusion...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723002449 |
| _version_ | 1811155481235816448 |
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| author | Haifeng Lu Shujun Chen Qianqian Nie Qun Xue Hua Fan Yiqing Wang Shenghao Fan Juehua Zhu Haitao Shen Haiying Li Qi Fang Jianqiang Ni Gang Chen |
| author_facet | Haifeng Lu Shujun Chen Qianqian Nie Qun Xue Hua Fan Yiqing Wang Shenghao Fan Juehua Zhu Haitao Shen Haiying Li Qi Fang Jianqiang Ni Gang Chen |
| author_sort | Haifeng Lu |
| collection | DOAJ |
| description | Summary: Synaptotagmin III (Syt3) is a Ca2+-dependent membrane-traffic protein that is highly concentrated in synaptic plasma membranes and affects synaptic plasticity by regulating post-synaptic receptor endocytosis. Here, we show that Syt3 is upregulated in the penumbra after ischemia/reperfusion (I/R) injury. Knockdown of Syt3 protects against I/R injury, promotes recovery of motor function, and inhibits cognitive decline. Overexpression of Syt3 exerts the opposite effects. Mechanistically, I/R injury augments Syt3-GluA2 interactions, decreases GluA2 surface expression, and promotes the formation of Ca2+-permeable AMPA receptors (CP-AMPARs). Using a CP-AMPAR antagonist or dissociating the Syt3-GluA2 complex via TAT-GluA2-3Y peptide promotes recovery from neurological impairments and improves cognitive function. Furthermore, Syt3 knockout mice are resistant to cerebral ischemia because they show high-level expression of surface GluA2 and low-level expression of CP-AMPARs after I/R. Our results indicate that Syt3-GluA2 interactions, which regulate the formation of CP-AMPARs, may be a therapeutic target for ischemic insults. |
| first_indexed | 2024-04-10T04:34:58Z |
| format | Article |
| id | doaj.art-44f5ceb0ed514f2789d394375d389f63 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T04:34:58Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-44f5ceb0ed514f2789d394375d389f632023-03-10T04:34:52ZengElsevierCell Reports2211-12472023-03-01423112233Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in strokeHaifeng Lu0Shujun Chen1Qianqian Nie2Qun Xue3Hua Fan4Yiqing Wang5Shenghao Fan6Juehua Zhu7Haitao Shen8Haiying Li9Qi Fang10Jianqiang Ni11Gang Chen12Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, China; Corresponding authorThe First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471000, Henan, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Institute of Stroke Research, Soochow University, Suzhou 215006, Jiangsu, China; Corresponding authorSummary: Synaptotagmin III (Syt3) is a Ca2+-dependent membrane-traffic protein that is highly concentrated in synaptic plasma membranes and affects synaptic plasticity by regulating post-synaptic receptor endocytosis. Here, we show that Syt3 is upregulated in the penumbra after ischemia/reperfusion (I/R) injury. Knockdown of Syt3 protects against I/R injury, promotes recovery of motor function, and inhibits cognitive decline. Overexpression of Syt3 exerts the opposite effects. Mechanistically, I/R injury augments Syt3-GluA2 interactions, decreases GluA2 surface expression, and promotes the formation of Ca2+-permeable AMPA receptors (CP-AMPARs). Using a CP-AMPAR antagonist or dissociating the Syt3-GluA2 complex via TAT-GluA2-3Y peptide promotes recovery from neurological impairments and improves cognitive function. Furthermore, Syt3 knockout mice are resistant to cerebral ischemia because they show high-level expression of surface GluA2 and low-level expression of CP-AMPARs after I/R. Our results indicate that Syt3-GluA2 interactions, which regulate the formation of CP-AMPARs, may be a therapeutic target for ischemic insults.http://www.sciencedirect.com/science/article/pii/S2211124723002449CP: Neuroscience |
| spellingShingle | Haifeng Lu Shujun Chen Qianqian Nie Qun Xue Hua Fan Yiqing Wang Shenghao Fan Juehua Zhu Haitao Shen Haiying Li Qi Fang Jianqiang Ni Gang Chen Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke Cell Reports CP: Neuroscience |
| title | Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke |
| title_full | Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke |
| title_fullStr | Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke |
| title_full_unstemmed | Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke |
| title_short | Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke |
| title_sort | synaptotagmin 3 interactions with glua2 mediate brain damage and impair functional recovery in stroke |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723002449 |
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