Development
Abstract
The balance among different subtypes of glutamate receptors (GluRs) is crucial for synaptic function and plasticity at excitatory synapses. However, the mechanisms balancing synaptic GluR subtypes remain unclear. Herein, we show that the two subtypes of GluRs A and B expressed atDrosophilaneuromuscular junction (NMJ) synapses mutually antagonize each other in terms of their relative synaptic levels, and affect sub-synaptic localisation of each other as shown by super-resolution microscopy. Upon temperature-shift induced NMJ plasticity, GluR subtype A increased but subtype B decreased in the course of hours. Inhibiting the activity of GluR subtype A leads to imbalance of GluR subtypes towards more GluRIIA.To further understand signalling pathways underlying the balance of GluR subtypes, we performed an RNAi screen of candidate genes and found that postsynaptic specific knockdown ofdunce, which encodes cAMP phosphodiesterase, increased A but decreased B GluR subtype levels. Furthermore, bidirectional alterations of postsynaptic cAMP signalling resulted in the same antagonistic regulation of the two GluR subtypes. Our findings thus identify a direct role of postsynaptic cAMP signalling in controlling the plasticity-related balance of GluRs.
| 论文编号: | DOI:10.1242/dev.191874 |
| 论文题目: | Postsynaptic cAMP Signalling Regulates the Antagonistic Balance of Glutamate Receptor Subtypes |
| 英文论文题目: | Postsynaptic cAMP Signalling Regulates the Antagonistic Balance of Glutamate Receptor Subtypes |
| 第一作者: | Kai Zhao, Huilin Hong, Lu Zhao, Sheng Huang, Ying Gao, Elsayed Metwally, Yuqiang Jiang, Stephan J. Sigrist, Yong Q. Zhang |
| 英文第一作者: | Kai Zhao, Huilin Hong, Lu Zhao, Sheng Huang, Ying Gao, Elsayed Metwally, Yuqiang Jiang, Stephan J. Sigrist, Yong Q. Zhang |
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| 发表年度: | 2020-11-27 |
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| 摘要: | The balance among different subtypes of glutamate receptors (GluRs) is crucial for synaptic function and plasticity at excitatory synapses. However, the mechanisms balancing synaptic GluR subtypes remain unclear. Herein, we show that the two subtypes of GluRs A and B expressed atDrosophilaneuromuscular junction (NMJ) synapses mutually antagonize each other in terms of their relative synaptic levels, and affect sub-synaptic localisation of each other as shown by super-resolution microscopy. Upon temperature-shift induced NMJ plasticity, GluR subtype A increased but subtype B decreased in the course of hours. Inhibiting the activity of GluR subtype A leads to imbalance of GluR subtypes towards more GluRIIA.To further understand signalling pathways underlying the balance of GluR subtypes, we performed an RNAi screen of candidate genes and found that postsynaptic specific knockdown ofdunce, which encodes cAMP phosphodiesterase, increased A but decreased B GluR subtype levels. Furthermore, bidirectional alterations of postsynaptic cAMP signalling resulted in the same antagonistic regulation of the two GluR subtypes. Our findings thus identify a direct role of postsynaptic cAMP signalling in controlling the plasticity-related balance of GluRs. |
| 英文摘要: | The balance among different subtypes of glutamate receptors (GluRs) is crucial for synaptic function and plasticity at excitatory synapses. However, the mechanisms balancing synaptic GluR subtypes remain unclear. Herein, we show that the two subtypes of GluRs A and B expressed atDrosophilaneuromuscular junction (NMJ) synapses mutually antagonize each other in terms of their relative synaptic levels, and affect sub-synaptic localisation of each other as shown by super-resolution microscopy. Upon temperature-shift induced NMJ plasticity, GluR subtype A increased but subtype B decreased in the course of hours. Inhibiting the activity of GluR subtype A leads to imbalance of GluR subtypes towards more GluRIIA.To further understand signalling pathways underlying the balance of GluR subtypes, we performed an RNAi screen of candidate genes and found that postsynaptic specific knockdown ofdunce, which encodes cAMP phosphodiesterase, increased A but decreased B GluR subtype levels. Furthermore, bidirectional alterations of postsynaptic cAMP signalling resulted in the same antagonistic regulation of the two GluR subtypes. Our findings thus identify a direct role of postsynaptic cAMP signalling in controlling the plasticity-related balance of GluRs. |
| 刊物名称: | Development |
| 英文刊物名称: | Development |
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| 其它备注: | Kai Zhao, Huilin Hong, Lu Zhao, Sheng Huang, Ying Gao, Elsayed Metwally, Yuqiang Jiang, Stephan J. Sigrist, Yong Q. Zhang. Postsynaptic cAMP Signalling Regulates the Antagonistic Balance of Glutamate Receptor Subtypes. Development. DOI: 10.1242/dev.191874 |
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