Proteomics, Ultrastructure, and Physiology of Hippocampal Synapses in a Fragile X Syndrome Mouse Model Reveal Presynaptic Phenotype
Proteomics, Ultrastructure, and Physiology of Hippocampal Synapses in a Fragile X Syndrome Mouse Model Reveal Presynaptic Phenotype
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DOI：
10.1074/jbc.m110.210260
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发表时间：
2011-07-22
影响因子：
4.8
通讯作者：
Li, Ka Wan
中科院分区：
文献类型：
--
作者：
Klemmer, Patricia;Meredith, Rhiannon M.;Li, Ka Wan
脆性X综合征（FXS）是遗传性智力低下的最常见形式，由编码脆性X智力低下蛋白（FMRP）的Fmr1基因的功能缺失突变引起。FMRP影响树突状蛋白的合成，从而导致突触异常。在这里，我们在FXS小鼠模型中使用定量蛋白质组学方法来揭示海马突触蛋白水平的变化。使用两组8重iTRAQ实验分析了16个独立的Fmr1敲除小鼠和野生型小鼠库。在两个iTRAQ系列中用至少三种不同的肽定量的205种蛋白质中，有23种蛋白质的丰度在Fmr1敲除和野生型突触之间存在差异，具有错误发现率（q值）
Fragile X syndrome (FXS), the most common form of hereditary mental retardation, is caused by a loss-of-function mutation of the Fmr1 gene, which encodes fragile X mental retardation protein (FMRP). FMRP affects dendritic protein synthesis, thereby causing synaptic abnormalities. Here, we used a quantitative proteomics approach in an FXS mouse model to reveal changes in levels of hippocampal synapse proteins. Sixteen independent pools of Fmr1 knock-out mice and wild type mice were analyzed using two sets of 8-plex iTRAQ experiments. Of 205 proteins quantified with atleast three distinct peptides in both iTRAQ series, the abundance of 23 proteins differed between Fmr1 knock-out and wild type synapses with a false discovery rate (q-value)