title: Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory.
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-specificSnx6knockout 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.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.|Graduate School, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.|State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.|MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, China.|Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.|Graduate School, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|Graduate School, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.|Graduate School, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Chenchang
authors.initials: C
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiahe
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.|MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, China.|Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Yun S
authors.initials: YS
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jia-Jia
authors.identifier: 0000-0002-6099-1059
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D000072233:Homer Scaffolding Proteins / Q000378:metabolism; D018345:Mice, Knockout; D017966:Pyramidal Cells / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism; D058305:Sorting Nexins / Q000172:deficiency* / Q000378:metabolism; D065852:Spatial Memory; D013569:Synapses / Q000502:physiology*
chemical_list: D000072233:Homer Scaffolding Proteins; D017470:Receptors, Glutamate; C532245:SNX6 protein, mouse; D058305:Sorting Nexins
keywords: AMPAR; Homer1b/c; SNX6; cell biology; dendritic distribution; dendritic spine; mouse; neuroscience; spatial memory