Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory
Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory
复制标题
SNX6 的消融导致 CA1 锥体神经元突触功能和空间记忆缺陷
DOI：
10.7554/elife.20991
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发表时间：
2017-01-30
期刊：
影响因子：
7.7
通讯作者：
Liu, Jia-Jia
中科院分区：
文献类型：
--
作者：
Niu, Yang;Dai, Zhanghua;Liu, Jia-Jia
SNX6是一种普遍表达的PX-bar蛋白，在逆转录病毒介导的囊泡逆行转运过程中发挥重要作用。在此，我们报道了CNS特异性Snx6基因敲除小鼠表现出空间学习和记忆缺陷，并伴有海马CA1区锥体细胞远端树突棘的丢失。SNX6与Hmer 1b/c相互作用，Hmer 1b/c是突触后支架蛋白，对突触后密度(PSD)蛋白的突触分布和树突棘的结构完整性至关重要。我们证明SNX6独立于逆转录单体发挥作用，调节Hmer 1b/c在树突轴中的分布。我们还发现Hmer 1b/c通过蛋白质扩散从茎向刺转移，这不需要SNX6。消融SNX6可导致远端树突状细胞Hmer 1b/c分布减少，AMPAR表面水平降低，AMPAR介导的突触传递功能受损。这些发现揭示了SNX6在中枢神经系统兴奋性神经元中的生理作用。DOI：http://dx.doi.org/10.7554/eLife.20991.001
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. DOI: http://dx.doi.org/10.7554/eLife.20991.001