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ALS和FTD中FUS的修改及其影响
Modifications of FUS and implications in ALS and FTD |
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| 课程网址: |
http://videolectures.net/snc2015_darovic_modifications_and_implic...
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| 主讲教师: |
Simona Darovic
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| 开课单位: |
约瑟夫·斯特凡研究所
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| 开课时间: |
2015-10-01
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| 课程语种: |
英语
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| 中文简介: |
额颞叶变性（FTLD）和肌萎缩侧索硬化（ALS）是临床、遗传和神经病理学重叠的神经退行性疾病。FUS的异常细胞质聚集（在肉瘤中融合）与3%的家族性ALS和10%的所有FTLD病例（FTLD-FUS）相关。FUS是一种核RNA/DNA结合蛋白，其C端存在PY型核定位信号，可与转运蛋白-1相互作用并转运至细胞核。具有FUS阳性胞质包涵体的ALS患者包含编码FUS的基因突变。这些突变中的大多数属于核定位信号，这使其无法运输到细胞核。另一方面，FTLD-FUS患者没有FUS突变，但FUS仍在细胞质包涵体中积累，表明ALS和FTLD包涵体形成的机制不同。我们的目的是了解FUS的核定位信号是否受到翻译后修饰的影响。我们在FUS的核定位信号中发现了一种新的翻译后修饰。这种修饰破坏了与转运蛋白-1的相互作用，从而影响FUS进入细胞核的转运。我们的研究表明，新的翻译后修饰是调节和潜在干扰ALS和FTLD中FUS核转运的机制之一。
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| 课程简介: |
Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders with clinical, genetic, and neuropathological overlap. Aberrant cytoplasmic aggregation of FUS (fused in sarcoma) is associated with 3% of familial ALS and 10% of all FTLD cases (FTLD-FUS). FUS is a nuclear RNA/DNA binding protein with PY type nuclear localization signal present at its C-terminus which enables interaction with Transportin-1 and its transport into the nucleus. ALS patients with FUS positive cytoplasmic inclusions contain mutations in gene encoding FUS. The majority of these mutations fall within the nuclear localization signal which disables its transport to nucleus. On the other hand, patients with FTLD-FUS do not have FUS mutations but FUS still accumulates in cytoplasmic inclusions, suggesting a different mechanism of inclusion formation in ALS and FTLD. Our aim is to find out whether nuclear localization signal of FUS is subjected to posttranslational modifications that have impact on its localization. We have identified a novel posttranslational modification in nuclear localisation signal of FUS. This modification destroys interaction with Transportin-1 and consequentially affects transport of FUS into the nucleus. Our study implicates new posttranslational modifications as one of the mechanisms by which nuclear transport of FUS is regulated and potentially perturbed in ALS and FTLD.
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| 关 键 词: |
额颞叶变性; 核定位信号; 核转运
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| 课程来源: |
视频讲座网
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| 数据采集: |
2021-12-11：nkq
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| 最后编审: |
2021-12-11：nkq
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| 阅读次数: |
55
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