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Ablation of SNX6 Leads to Defects in Synaptic Function of CA1 Pyramidal Neurons and Spatial Memory
Yang Niu, Zhonghua Dai, Wenxue Liu, Cheng Zhang, Yanrui Yang, Zhenzhen Guo, Xiaoyu Li, Chenchang Xu, Xiahe Huang, Yingchun Wang, Yun S. Shi, Jia-Jia Liu
eLife
Abstract
SNX6 is a ubiquitously expressed PX-BAR protein that plays important roles in retromer-mediated retrograde vesicular transport from endosomes. Here we report that CNS-specific Snx6 knockout mice exhibit deficits in spatial learning and memory, accompanied with loss of spines from distal dendrites of hippocampal CA1 pyramidal cells. SNX6 interacts with Homer1b/c, a postsynaptic scaffold protein crucial for synaptic distribution of other postsynaptic density (PSD) proteins and structural integrity of dendritic spines. We show that SNX6 functions independently of retromer to regulate distribution of Homer1b/c in the dendritic shaft. We also find that Homer1b/c translocates from shaft to spines by protein diffusion, which does not require SNX6. Ablation of SNX6 causes reduced distribution of Homer1b/c in distal dendrites, decrease in surface levels of AMPAR and impaired AMPAR-mediated synaptic transmission. These findings reveal a physiological role of SNX6 in CNS excitatory neurons.
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论文编号: |
DOI:10.7554/eLife.20991 |
论文题目: |
Ablation of SNX6 Leads to Defects in Synaptic Function of CA1 Pyramidal Neurons and Spatial Memory |
英文论文题目: |
Ablation of SNX6 Leads to Defects in Synaptic Function of CA1 Pyramidal Neurons and Spatial Memory |
第一作者: |
Yang Niu, Zhonghua Dai, Wenxue Liu, Cheng Zhang, Yanrui Yang, Zhenzhen Guo, Xiaoyu Li, Chenchang Xu, Xiahe Huang, Yingchun Wang, Yun S. Shi, Jia-Jia Liu |
英文第一作者: |
Yang Niu, Zhonghua Dai, Wenxue Liu, Cheng Zhang, Yanrui Yang, Zhenzhen Guo, Xiaoyu Li, Chenchang Xu, Xiahe Huang, Yingchun Wang, Yun S. Shi, Jia-Jia Liu |
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2017-02-08 |
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SNX6 is a ubiquitously expressed PX-BAR protein that plays important roles in retromer-mediated retrograde vesicular transport from endosomes. Here we report that CNS-specific Snx6 knockout mice exhibit deficits in spatial learning and memory, accompanied with loss of spines from distal dendrites of hippocampal CA1 pyramidal cells. SNX6 interacts with Homer1b/c, a postsynaptic scaffold protein crucial for synaptic distribution of other postsynaptic density (PSD) proteins and structural integrity of dendritic spines. We show that SNX6 functions independently of retromer to regulate distribution of Homer1b/c in the dendritic shaft. We also find that Homer1b/c translocates from shaft to spines by protein diffusion, which does not require SNX6. Ablation of SNX6 causes reduced distribution of Homer1b/c in distal dendrites, decrease in surface levels of AMPAR and impaired AMPAR-mediated synaptic transmission. These findings reveal a physiological role of SNX6 in CNS excitatory neurons. |
英文摘要: |
SNX6 is a ubiquitously expressed PX-BAR protein that plays important roles in retromer-mediated retrograde vesicular transport from endosomes. Here we report that CNS-specific Snx6 knockout mice exhibit deficits in spatial learning and memory, accompanied with loss of spines from distal dendrites of hippocampal CA1 pyramidal cells. SNX6 interacts with Homer1b/c, a postsynaptic scaffold protein crucial for synaptic distribution of other postsynaptic density (PSD) proteins and structural integrity of dendritic spines. We show that SNX6 functions independently of retromer to regulate distribution of Homer1b/c in the dendritic shaft. We also find that Homer1b/c translocates from shaft to spines by protein diffusion, which does not require SNX6. Ablation of SNX6 causes reduced distribution of Homer1b/c in distal dendrites, decrease in surface levels of AMPAR and impaired AMPAR-mediated synaptic transmission. These findings reveal a physiological role of SNX6 in CNS excitatory neurons. |
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eLife |
英文刊物名称: |
eLife |
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其它备注: |
Yang Niu, Zhonghua Dai, Wenxue Liu, Cheng Zhang, Yanrui Yang, Zhenzhen Guo, Xiaoyu Li, Chenchang Xu, Xiahe Huang, Yingchun Wang, Yun S. Shi, Jia-Jia Liu. Ablation of SNX6 Leads to Defects in Synaptic Function of CA1 Pyramidal Neurons and Spatial Memory. eLife. DOI:10.7554/eLife.20991 |
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