The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus
Summary: Complement-dependent microglia pruning of excitatory synapses has been widely reported in physiological and pathological conditions, with few reports concerning pruning of inhibitory synapses or direct regulation of synaptic transmission by complement components. Here, we report that loss o...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723003601 |
| _version_ | 1797850912070303744 |
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| author | Lang Wen Xiaoli Yang Zujun Wu Shumei Fu Yaxi Zhan Zuolong Chen Danlei Bi Yong Shen |
| author_facet | Lang Wen Xiaoli Yang Zujun Wu Shumei Fu Yaxi Zhan Zuolong Chen Danlei Bi Yong Shen |
| author_sort | Lang Wen |
| collection | DOAJ |
| description | Summary: Complement-dependent microglia pruning of excitatory synapses has been widely reported in physiological and pathological conditions, with few reports concerning pruning of inhibitory synapses or direct regulation of synaptic transmission by complement components. Here, we report that loss of CD59, an important endogenous inhibitor of the complement system, leads to compromised spatial memory performance. Furthermore, CD59 deficiency impairs GABAergic synaptic transmission in the hippocampal dentate gyrus (DG). This depends on regulation of GABA release triggered by Ca2+ influx through voltage-gated calcium channels (VGCCs) rather than inhibitory synaptic pruning by microglia. Notably, CD59 colocalizes with inhibitory pre-synaptic terminals and regulates SNARE complex assembly. Together, these results demonstrate that the complement regulator CD59 plays an important role in normal hippocampal function. |
| first_indexed | 2024-04-09T19:09:17Z |
| format | Article |
| id | doaj.art-83c3394af03d4200932eb1f61b549d23 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T19:09:17Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-83c3394af03d4200932eb1f61b549d232023-04-07T06:50:12ZengElsevierCell Reports2211-12472023-04-01424112349The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrusLang Wen0Xiaoli Yang1Zujun Wu2Shumei Fu3Yaxi Zhan4Zuolong Chen5Danlei Bi6Yong Shen7Department of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou 215000, ChinaDepartment of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Anhui Province Key Laboratory of Biomedical Aging Research, University of Science and Technology of China, Hefei 230026, China; Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230026, China; CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; Corresponding authorDepartment of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Anhui Province Key Laboratory of Biomedical Aging Research, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; Corresponding authorSummary: Complement-dependent microglia pruning of excitatory synapses has been widely reported in physiological and pathological conditions, with few reports concerning pruning of inhibitory synapses or direct regulation of synaptic transmission by complement components. Here, we report that loss of CD59, an important endogenous inhibitor of the complement system, leads to compromised spatial memory performance. Furthermore, CD59 deficiency impairs GABAergic synaptic transmission in the hippocampal dentate gyrus (DG). This depends on regulation of GABA release triggered by Ca2+ influx through voltage-gated calcium channels (VGCCs) rather than inhibitory synaptic pruning by microglia. Notably, CD59 colocalizes with inhibitory pre-synaptic terminals and regulates SNARE complex assembly. Together, these results demonstrate that the complement regulator CD59 plays an important role in normal hippocampal function.http://www.sciencedirect.com/science/article/pii/S2211124723003601CP: Neuroscience |
| spellingShingle | Lang Wen Xiaoli Yang Zujun Wu Shumei Fu Yaxi Zhan Zuolong Chen Danlei Bi Yong Shen The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus Cell Reports CP: Neuroscience |
| title | The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus |
| title_full | The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus |
| title_fullStr | The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus |
| title_full_unstemmed | The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus |
| title_short | The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus |
| title_sort | complement inhibitor cd59 is required for gabaergic synaptic transmission in the dentate gyrus |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723003601 |
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