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

doi:10.7554/eLife.20991

Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory

Elife. 2017 Jan 30:6:e20991. doi: 10.7554/eLife.20991.

Authors

Yang Niu^{1

2

3}, Zhonghua Dai^{1

2}, Wenxue Liu^{4

5

6

7}, Cheng Zhang^{1

2}, Yanrui Yang^{1

2}, Zhenzhen Guo^{1

2

3}, Xiaoyu Li^{1

3}, Chenchang Xu^{1

2

3}, Xiahe Huang¹, Yingchun Wang¹, Yun S Shi^{5

6

7}, Jia-Jia Liu^{1

2}

Affiliations

¹ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
² CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
³ Graduate School, University of Chinese Academy of Sciences, Beijing, China.
⁴ Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
⁵ State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
⁶ MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, China.
⁷ Model Animal Research Center, Nanjing University, Nanjing, 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 the 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.

Keywords: AMPAR; Homer1b/c; SNX6; cell biology; dendritic distribution; dendritic spine; mouse; neuroscience; spatial memory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CA1 Region, Hippocampal / physiology*
Homer Scaffolding Proteins / metabolism
Mice, Knockout
Pyramidal Cells / physiology*
Receptors, Glutamate / metabolism
Sorting Nexins / deficiency*
Sorting Nexins / metabolism
Spatial Memory*
Synapses / physiology*

Substances

Homer Scaffolding Proteins
Receptors, Glutamate
SNX6 protein, mouse
Sorting Nexins

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.