Gene expression pattern Identification and characterization of the Drosophila tau homolog
Gene expression pattern Identification and characterization of the Drosophila tau homolog
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发表时间：
2001
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通讯作者：
G. Heidary;M. Fortini
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作者：
G. Heidary;M. Fortini
包括阿尔茨海默病和一组临床异质性额颞叶痴呆在内的神经退行性病变的病理标志是细胞内神经原纤维蛋白病变的存在（见Spillantini和Goedert， TINS 10(1998) 428）。这些结构的主要成分是微管相关蛋白tau。虽然tau通常是一种富含轴突的高可溶性蛋白，但在这些沉积物中，它异常地过度磷酸化，不溶性，并重新分配到神经元的体突隔室。通过超微结构分析，已经确定这些病变中的tau蛋白是丝状的，并组织成对螺旋细丝、直细丝或带状细丝（Goedert et al., the Molecular and Genetic Basis of Neurological Disease(1997) 613）。通过微管的动态结合，tau被认为可以促进轴突的结构稳定性，但目前尚不清楚tau聚集体是否通过对正常细胞功能（如细胞器运输）的直接毒性或对微管稳定性的间接影响来促进神经变性。在家族性额颞叶痴呆和帕金森病患者中发现与17号染色体相关的tau基因突变，表明tau基因突变足以引起神经退行性疾病(Poorkaj等人，Ann。神经科杂志。43 (1998)815；Hutton et al., Nature 393(1998) 702)。为了阐明tau功能障碍导致神经元丧失的机制，我们试图在遗传易感的生物体中模拟人类tau病。在这里，我们描述了果蝇tau cDNA （GenBank登录号AY032977）的分离，识别编码蛋白的抗体的产生，以及它们在确定果蝇tau蛋白的表达和亚细胞定位中的应用。2001爱思唯尔科学爱尔兰有限公司版权所有。
A pathological hallmark of neurodegenerative tauopathies, including Alzheimer’s disease and a group of clinically heterogeneous frontotemporal dementias, is the presence of intracellular neurofibrillary protein lesions (reviewed in Spillantini and Goedert, TINS 10 (1998) 428). The principal component of these structures is the microtubule-associated protein tau. Although tau is normally a highly soluble protein enriched in axons, in these deposits, it is abnormally hyperphosphorylated, insoluble, and redistributed to the somatodendritic compartments of neurons. Through ultrastructual analyses, it has been determined that the tau protein in these lesions is filamentous and organized into paired-helical filaments, straight filaments, or ribbon-like filaments (Goedert et al., The Molecular and Genetic Basis of Neurological Disease (1997) 613). By the dynamic binding of microtubules, tau is thought to promote the structural stability of axons, but whether tau aggregates contribute to neurodegeneration through a direct toxicity on normal cellular functions such as organelle transport or an indirect effect on microtubule stability, is currently unknown. The identification of mutations in the tau locus in patients with familial frontotemporal dementia and Parkinsonism linked to chromosome 17 has demonstrated that mutations in tau are sufficient to cause neurodegenerative disease (Poorkaj et al., Ann. Neurol. 43 (1998) 815; Hutton et al., Nature 393 (1998) 702). To elucidate the mechanisms by which tau dysfunction contributes to neuronal loss, we have sought to model human tauopathies in a genetically tractable organism. Here we describe the isolation of a Drosophila tau cDNA (GenBank accession number AY032977), the production of antibodies that recognize the encoded protein, and their use in determining the expression and subcellular localization of the fly tau protein. q 2001 Elsevier Science Ireland Ltd. All rights reserved.