Several novel nuclear envelope transmembrane proteins identified in skeletal muscle have cytoskeletal associations.
Several novel nuclear envelope transmembrane proteins identified in skeletal muscle have cytoskeletal associations.
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DOI：
10.1074/mcp.m110.003129
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Schirmer EC
中科院分区：
文献类型：
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作者：
Wilkie GS;Korfali N;Swanson SK;Malik P;Srsen V;Batrakou DG;de las Heras J;Zuleger N;Kerr AR;Florens L;Schirmer EC
来自肝脏和神经母细胞瘤细胞系的核膜先前已经通过蛋白质组学进行了分析;然而，与核膜相关的大多数疾病都会影响肌肉。为了确定肌肉是否具有独特的核膜蛋白，制备了大鼠骨骼肌核膜，并采用多维蛋白鉴定技术进行了分析。许多新的肌肉特异性蛋白质被确定，没有出现在以前的核膜数据集。其中11个通过融合蛋白的表达和肌肉组织冷冻切片的抗体染色证实了核膜驻留。此外，转录水平的几个新确定的核膜跨膜蛋白增加肌肉分化过程中使用小鼠和人在体外模型系统。其中一些蛋白质在间期细胞的核表面与微管一起追踪，并在有丝分裂细胞的微管纺锤体基部积累，这表明它们可能与连接细胞核和细胞骨架的复合物有关。骨骼肌核膜蛋白质组中组织特异性蛋白质的发现表明了分析与疾病相关的所有组织的核膜的重要性，并表明对细胞器蛋白质组中组织差异的一般调查可能会产生关键的见解。
Nuclear envelopes from liver and a neuroblastoma cell line have previously been analyzed by proteomics; however, most diseases associated with the nuclear envelope affect muscle. To determine whether muscle has unique nuclear envelope proteins, rat skeletal muscle nuclear envelopes were prepared and analyzed by multidimensional protein identification technology. Many novel muscle-specific proteins were identified that did not appear in previous nuclear envelope data sets. Nuclear envelope residence was confirmed for 11 of these by expression of fusion proteins and by antibody staining of muscle tissue cryosections. Moreover, transcript levels for several of the newly identified nuclear envelope transmembrane proteins increased during muscle differentiation using mouse and human in vitro model systems. Some of these proteins tracked with microtubules at the nuclear surface in interphase cells and accumulated at the base of the microtubule spindle in mitotic cells, suggesting they may associate with complexes that connect the nucleus to the cytoskeleton. The finding of tissue-specific proteins in the skeletal muscle nuclear envelope proteome argues the importance of analyzing nuclear envelopes from all tissues linked to disease and suggests that general investigation of tissue differences in organellar proteomes might yield critical insights.