The RNA-binding motif 45 (RBM45) protein accumulates in inclusion bodies in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) patients.
The RNA-binding motif 45 (RBM45) protein accumulates in inclusion bodies in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) patients.
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DOI：
10.1007/s00401-012-1045-x
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发表时间：
2012-11
影响因子：
12.7
通讯作者：
Bowser R
中科院分区：
文献类型：
--
作者：
Collins M;Riascos D;Kovalik T;An J;Krupa K;Krupa K;Hood BL;Conrads TP;Renton AE;Traynor BJ;Bowser R
目前，RNA结合蛋白病理学是肌萎缩侧索硬化症(ALS)和TDP-43或FUS病理(FTLD-TDP和FTLD-FUS)的额颞叶变性患者最具特征性的病理特征之一。我们用液相色谱-串联质谱仪检测了ALS患者脑脊液中RNA结合基序45(RBM45)蛋白的变化。该蛋白与ALS和FTLD-TDP或FTLD-FUS患者细胞质内含的TAR DNA结合蛋白43(TDP-43)和肉瘤融合蛋白(FUS)具有序列相似性。为了进一步确定RBM45的特征，我们首先用免疫印迹法证实了在ALS患者的脑脊液和脊髓组织提取液中存在RBM45。接下来，我们用免疫组织化学方法检测了RBM45的亚细胞分布，并在大脑和脊髓的神经元和胶质细胞的细胞核内进行了点状染色观察。我们还在91%的ALS、100%的FTLD-TDP和75%的阿尔茨海默病(AD)病例中检测到RBM45胞浆内含物。在含有C9ORF72六核苷酸重复扩增的患者中观察到最广泛的RBM45病理。这些RBM45包涵体存在于脊髓运动神经元、胶质细胞和齿状回神经元中。通过共聚焦显微镜观察，RBM45与泛素和TDP-43共定位于包涵体中。在含有RBM45胞质包涵体的神经元中，我们经常在缺乏TDP-43或泛素的细胞核内检测到这种蛋白质。我们使用ALS和对照受试者脑脊液的蛋白质组筛选确定了RBM45作为候选生物标记物，并将这种RNA结合蛋白与ALS、FTLD-TDP和AD的包裹体病理联系起来。本文的在线版本(doi：10.1007/s00401-0121045-x)包含补充材料，授权用户可以使用。
RNA-binding protein pathology now represents one of the best characterized pathologic features of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration patients with TDP-43 or FUS pathology (FTLD-TDP and FTLD-FUS). Using liquid chromatography tandem mass spectrometry, we identified altered levels of the RNA-binding motif 45 (RBM45) protein in the cerebrospinal fluid (CSF) of ALS patients. This protein contains sequence similarities to TAR DNA-binding protein 43 (TDP-43) and fused-in-sarcoma (FUS) that are contained in cytoplasmic inclusions of ALS and FTLD-TDP or FTLD-FUS patients. To further characterize RBM45, we first verified the presence of RBM45 in CSF and spinal cord tissue extracts of ALS patients by immunoblot. We next used immunohistochemistry to examine the subcellular distribution of RBM45 and observed in a punctate staining pattern within nuclei of neurons and glia in the brain and spinal cord. We also detected RBM45 cytoplasmic inclusions in 91 % of ALS, 100 % of FTLD-TDP and 75 % of Alzheimer’s disease (AD) cases. The most extensive RBM45 pathology was observed in patients that harbor the C9ORF72 hexanucleotide repeat expansion. These RBM45 inclusions were observed in spinal cord motor neurons, glia and neurons of the dentate gyrus. By confocal microscopy, RBM45 co-localizes with ubiquitin and TDP-43 in inclusion bodies. In neurons containing RBM45 cytoplasmic inclusions we often detected the protein in a punctate pattern within the nucleus that lacked either TDP-43 or ubiquitin. We identified RBM45 using a proteomic screen of CSF from ALS and control subjects for candidate biomarkers, and link this RNA-binding protein to inclusion pathology in ALS, FTLD-TDP and AD. The online version of this article (doi:10.1007/s00401-012-1045-x) contains supplementary material, which is available to authorized users.
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影响因子：
12.7
作者：
Al-Sarraj, Safa;King, Andrew;Shaw, Christopher E.
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Shaw, Christopher E.
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通讯作者：
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通讯作者：
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Rademakers R