Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory
- Chinese Academy of Sciences, China
- Nanjing University, China
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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Funding
National Natural Science Foundation of China (31530039 31325017 31471334)
- Yang Niu
- Zhonghua Dai
- Cheng Zhang
- Yanrui Yang
- Zhenzhen Guo
- Xiaoyu Li
- Jia-Jia Liu
Ministry of Science and Technology of the People's Republic of China (2014CB942802 2016YFA0500100 2014CB942804)
- Yang Niu
- Zhonghua Dai
- Wenxue Liu
- Cheng Zhang
- Yanrui Yang
- Zhenzhen Guo
- Xiaoyu Li
- Yun S Shi
- Jia-Jia Liu
State Key Laboratory of Molecular Developmental Biology, China (2014-MDB-TS-01)
- Yang Niu
- Zhonghua Dai
- Cheng Zhang
- Yanrui Yang
- Zhenzhen Guo
- Xiaoyu Li
- Xiahe Huang
- Yingchun Wang
- Jia-Jia Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in compliance with the guidelines of the Animal Care and Use committee of the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (Permit Number: AP2013001). All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.
Copyright
© 2017, Niu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory
eLife 6:e20991.
https://doi.org/10.7554/eLife.20991
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