Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders
Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders
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DOI：
10.1016/s0169-328x(99)00079-0
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发表时间：
1999-05-07
期刊：
影响因子：
--
通讯作者：
Arendt, T
中科院分区：
文献类型：
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作者：
Janke, C;Beck, M;Arendt, T
微管相关蛋白 tan 通过与微管相互作用来调节神经元细胞骨架的动态稳定性。它由单个基因编码，但由于 RNA 剪接的差异而以多种亚型表达。人类中枢神经系统中存在六种异构体。这些亚型的不同之处在于促进微管组装的能力以及稳定现有微管结构的能力。此外，tau 的一些亚型特别参与神经退行性疾病的发病机制。因此，tau蛋白的剪接可能会严重影响tau蛋白的生理功能以及tau蛋白病神经退行性疾病的发病机制。本研究探讨了 tau 的 6 种亚型在包括智人在内的 12 种哺乳动物的中枢神经系统中的差异表达。六种 tau 异构体的出现情况差异很大。然而，系统发育相关的物种表达了类似的 tau 亚型模式。这些结果表明剪接范式的系统发育下降，可以与基于形态学和分子遗传学研究的已知系统发育概念相匹配。特别是，人类中枢神经系统中 tan 亚型的独特表达模式可能与人类对 tau 蛋白病神经退行性疾病（即阿尔茨海默氏病、额颞叶痴呆和皮克氏病）的特别脆弱性有关。 (C) 1999 Elsevier Science B.V. 保留所有权利。
The microtubule-associated protein tan regulates the dynamic stability of the neuronal cytoskeleton by interacting with microtubules. It is encoded by a single gene, but expressed in a Variety of isoforms due to differential RNA splicing. Six isoforms can be found in the human central nervous system. These isoforms differ in their ability to promote the assembly of microtubules as well as in their capacity to stabilize existing microtubule structures. Furthermore, some of the isoforms of tau are specifically involved in the pathogenesis of neurodegenerative disorders. Thus, splicing of tau might critically influence the physiological functions of tau protein as well as the pathogenesis of neurodegenerative diseases with tauopathy. The present study addresses the differential expression of the six isoforms of tau in the central nervous system of 12 mammalian species including Homo sapiens. The occurrence of each of the six tau isoforms was highly variable. However, species that were phylogenetically related expressed a similar pattern of tau isoforms. These results suggest a phylogenetic descent of splicing paradigms, which can be matched with known phylogenetic concepts based on morphological and molecular genetical studies. Especially, the unique expression pattern of tan isoforms in the human central nervous system implicates a possible Link to the particular vulnerability of humans to neurodegenerative disorders with tauopathy, namely Alzheimer's disease, frontotemporal dementia and Pick's disease. (C) 1999 Elsevier Science B.V. All rights reserved.