Single particle analysis of tau oligomer formation induced by metal ions and organic solvents
Single particle analysis of tau oligomer formation induced by metal ions and organic solvents
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DOI：
10.1016/j.bbrc.2011.06.135
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发表时间：
2011-07-22
影响因子：
3.1
通讯作者：
Giese, Armin
中科院分区：
文献类型：
--
作者：
Bader, Benedikt;Nuebling, Georg;Giese, Armin
tau蛋白的病理性聚集体存在于几种称为“tau蛋白病”的神经退行性疾病中。越来越多的证据表明，tau寡聚体种类，而不是大的淀粉样蛋白细胞质包涵体相关的组织病理学诊断可能是至关重要的细胞损伤和神经退行性变。三价金属离子和聚阴离子结构如肝素或花生四烯酸已显示诱导tau聚集。然而，对tau聚集的早期过程知之甚少。在这项研究中，我们应用荧光相关光谱（FCS）和扫描强荧光靶点（SIFT），以研究在单粒子水平上在纳摩尔蛋白浓度下tau蛋白的寡聚体形成。我们的研究结果表明，不同的tau寡聚体的形成是由三价金属离子Fe（3+）和Al（3+）和有机溶剂，如DMSO，分别诱导。而二价金属离子（Cu（2+）、Zn（2+）、Mn（2+）、Ca（2+）、Me）则无影响。虽然DMSO诱导的小tau寡聚体在溶液中相对稳定，但非离子去污剂可引发动态重塑。此外，Al（3+）诱导快速形成不同的低聚物物种的较大尺寸。我们的研究结果为早期tau寡聚化和聚集动力学提供了进一步的见解。(C)2011 Elsevier Inc. All rights reserved.
Pathological aggregates of tau protein are found in several neurodegenerative diseases termed 'tauopathies'. Increasing evidence indicates that tau oligomer species rather than the large amyloid cytoplasmic inclusions relevant for histopathological diagnosis might be crucial for cellular damage and neurodegeneration. Trivalent metal ions and polyanionic structures like heparin or arachidonic acid have been shown to induce tau aggregation. However, little is known about early processes of tau aggregation. In this study, we applied fluorescence correlation spectroscopy (FCS) and scanning for intensely fluorescent targets (SIFT) to investigate oligomer formation of tau protein at nanomolar protein concentrations at the single-particle level. Our results indicate that the formation of distinct tau oligomers is induced by the trivalent metal ions Fe(3+) and Al(3+) and by organic solvents like DMSO, respectively. In contrast, bivalent metal ions (Cu(2+), Zn(2+), Mn(2+), Ca(2+), me) had no effect. While DMSO-induced small tau oligomers are relatively stable in solution, dynamic remodeling can be initiated by non-ionic detergents. Moreover Al(3+) induces rapid formation of a different oligomer species of larger size. Our results provide further insights into early tau oligomerization and aggregation dynamics. (C) 2011 Elsevier Inc. All rights reserved.