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A Pre-synaptic Function of Shank Protein in Drosophila
Song Wu, Guangming Gan, Zhiping Zhang, Jie Sun, Qifu Wang, Zhongbao Gao, Meixiang Li, Shan Jin, Juan Huang, Ulrich Thomas, Yong-hui Jiang, Yan Li, Rui Tian and Yong Q. Zhang
The Journal of Neuroscience
Abstract
Human genetic studies support that loss of function mutations in the [highlight]SH[/highlight]3 domain and [highlight]ank[/highlight]yrin repeat containing family proteins (SHANK1-3), the large synaptic scaffolding proteins enriched at the postsynaptic density of excitatory synapses, are causative for autism spectrum disorder (ASD) and other neuropsychiatric disorders in humans. To better understand the in vivo functions of Shank and facilitate dissection of neuropathology associated with SHANK mutations in human, we generated multiple mutations in the Shank gene, the only member of the SHANK family in Drosophila melanogaster. Both male and female Shank null mutants were fully viable and fertile with no apparent morphological or developmental defects. Expression analysis revealed apparent enrichment of Shank in the neuropils of the central nervous system. Specifically, Shank co-expressed with another PSD scaffold protein, Homer, in the calyx of mushroom bodies (MBs) in the brain. Consistent with high expression in MB calyces, Shank mutants show an abnormal calyx structure and reduced olfactory acuity. These morphological and functional phenotypes were fully rescued by pan-neuronal re-expression of Shank, and only partially rescued by pre- but no rescue by post-synaptic re-expression of Shank. Our findings thus establish a previously unappreciated pre-synaptic function of Shank. Key words: Shank; synaptic function; autism; PSD; mushroom body calyx
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论文编号: |
DOI:10.1523/JNEUROSCI.0893-17.2017 |
论文题目: |
A Pre-synaptic Function of Shank Protein in Drosophila |
英文论文题目: |
A Pre-synaptic Function of Shank Protein in Drosophila |
第一作者: |
Song Wu, Guangming Gan, Zhiping Zhang, Jie Sun, Qifu Wang, Zhongbao Gao, Meixiang Li, Shan Jin, Juan Huang, Ulrich Thomas, Yong-hui Jiang, Yan Li, Rui Tian and Yong Q. Zhang |
英文第一作者: |
Song Wu, Guangming Gan, Zhiping Zhang, Jie Sun, Qifu Wang, Zhongbao Gao, Meixiang Li, Shan Jin, Juan Huang, Ulrich Thomas, Yong-hui Jiang, Yan Li, Rui Tian and Yong Q. Zhang |
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2017-11-03 |
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摘要: |
Human genetic studies support that loss of function mutations in the [highlight]SH[/highlight]3 domain and [highlight]ank[/highlight]yrin repeat containing family proteins (SHANK1-3), the large synaptic scaffolding proteins enriched at the postsynaptic density of excitatory synapses, are causative for autism spectrum disorder (ASD) and other neuropsychiatric disorders in humans. To better understand the in vivo functions of Shank and facilitate dissection of neuropathology associated with SHANK mutations in human, we generated multiple mutations in the Shank gene, the only member of the SHANK family in Drosophila melanogaster. Both male and female Shank null mutants were fully viable and fertile with no apparent morphological or developmental defects. Expression analysis revealed apparent enrichment of Shank in the neuropils of the central nervous system. Specifically, Shank co-expressed with another PSD scaffold protein, Homer, in the calyx of mushroom bodies (MBs) in the brain. Consistent with high expression in MB calyces, Shank mutants show an abnormal calyx structure and reduced olfactory acuity. These morphological and functional phenotypes were fully rescued by pan-neuronal re-expression of Shank, and only partially rescued by pre- but no rescue by post-synaptic re-expression of Shank. Our findings thus establish a previously unappreciated pre-synaptic function of Shank. Key words: Shank; synaptic function; autism; PSD; mushroom body calyx |
英文摘要: |
Human genetic studies support that loss of function mutations in the [highlight]SH[/highlight]3 domain and [highlight]ank[/highlight]yrin repeat containing family proteins (SHANK1-3), the large synaptic scaffolding proteins enriched at the postsynaptic density of excitatory synapses, are causative for autism spectrum disorder (ASD) and other neuropsychiatric disorders in humans. To better understand the in vivo functions of Shank and facilitate dissection of neuropathology associated with SHANK mutations in human, we generated multiple mutations in the Shank gene, the only member of the SHANK family in Drosophila melanogaster. Both male and female Shank null mutants were fully viable and fertile with no apparent morphological or developmental defects. Expression analysis revealed apparent enrichment of Shank in the neuropils of the central nervous system. Specifically, Shank co-expressed with another PSD scaffold protein, Homer, in the calyx of mushroom bodies (MBs) in the brain. Consistent with high expression in MB calyces, Shank mutants show an abnormal calyx structure and reduced olfactory acuity. These morphological and functional phenotypes were fully rescued by pan-neuronal re-expression of Shank, and only partially rescued by pre- but no rescue by post-synaptic re-expression of Shank. Our findings thus establish a previously unappreciated pre-synaptic function of Shank. Key words: Shank; synaptic function; autism; PSD; mushroom body calyx |
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The Journal of Neuroscience |
英文刊物名称: |
The Journal of Neuroscience |
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其它备注: |
Song Wu, Guangming Gan, Zhiping Zhang, Jie Sun, Qifu Wang, Zhongbao Gao, Meixiang Li, Shan Jin, Juan Huang, Ulrich Thomas, Yong-hui Jiang, Yan Li, Rui Tian and Yong Q. Zhang. A Pre-synaptic Function of Shank Protein in Drosophila. The Journal of Neuroscience. DOI:10.1523/JNEUROSCI.0893-17.2017 |
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