Loss of CENP-F Results in Dilated Cardiomyopathy with Severe Disruption of Cardiac Myocyte Architecture.
Loss of CENP-F Results in Dilated Cardiomyopathy with Severe Disruption of Cardiac Myocyte Architecture.
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DOI：
10.1038/s41598-018-25774-1
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发表时间：
2018-05-15
影响因子：
4.6
通讯作者：
Bader DM
中科院分区：
文献类型：
--
作者：
Manalo A;Schroer AK;Fenix AM;Shancer Z;Coogan J;Brolsma T;Burnette DT;Merryman WD;Bader DM
着丝粒结合蛋白F（CENP-F）是一种非常大且复杂的蛋白质，具有许多不同的结合伴侣，包括微管网络的组分。已经鉴定了许多影响不同细胞行为的CENP-F功能。重要的是，新出现的数据表明，CENP-F功能的丧失或获得对人类发育和疾病具有关键影响。然而，必须注意的是，在单个心肌细胞水平上检查CENP-F功能丧失对基本细胞行为的影响的数据缺失。为了解决我们知识中的这一差距，我们分析了缺乏CENP-F的心肌细胞的基本细胞结构和功能。我们发现了许多不同的结构异常，包括微管网络的破坏影响心肌细胞的关键特征。这是第一份将微管网络功能障碍与心肌病联系起来的报告。重要的是，我们还提供了CENP-F单核苷酸多态性（SNP）和人类心脏病之间直接联系的数据。在近似意义上，这些检查CENP-F功能的数据解释了这种遗传模型中心脏病的细胞基础，并且在更大的意义上，它们将有望提供一个平台，该领域可以在广泛的研究领域探索这种关键蛋白质的不同细胞结果。
Centromere-binding protein F (CENP-F) is a very large and complex protein with many and varied binding partners including components of the microtubule network. Numerous CENP-F functions impacting diverse cellular behaviors have been identified. Importantly, emerging data have shown that CENP-F loss- or gain-of-function has critical effects on human development and disease. Still, it must be noted that data at the single cardiac myocyte level examining the impact of CENP-F loss-of-function on fundamental cellular behavior is missing. To address this gap in our knowledge, we analyzed basic cell structure and function in cardiac myocytes devoid of CENP-F. We found many diverse structural abnormalities including disruption of the microtubule network impacting critical characteristics of the cardiac myocyte. This is the first report linking microtubule network malfunction to cardiomyopathy. Importantly, we also present data demonstrating a direct link between a CENP-F single nucleotide polymorphism (snp) and human cardiac disease. In a proximate sense, these data examining CENP-F function explain the cellular basis underlying heart disease in this genetic model and, in a larger sense, they will hopefully provide a platform upon which the field can explore diverse cellular outcomes in wide-ranging areas of research on this critical protein.
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影响因子：
37.8
作者：
Nagueh, SF;Shah, G;Granzier, HL
通讯作者：
Granzier, HL
影响因子：
37.8
作者：
Chaturvedi, Rajiv R.;Herron, Todd;Kentish, Jonathan C.
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影响因子：
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通讯作者：
Abate-Shen C
影响因子：
4.8
作者：
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通讯作者：
Sawyer, DB