Reversible Cation-Selective Attachment and Self-Assembly of Human Tau on Supported Brain Lipid Membranes,Nano Letters

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Reversible Cation-Selective Attachment and Self-Assembly of Human Tau on Supported Brain Lipid Membranes
Nano Letters ( IF 9.6 ) Pub Date : 2018-04-12 00:00:00 , DOI: 10.1021/acs.nanolett.8b01085
Stefania A. Mari ₁ , Susanne Wegmann ₂ , Katharina Tepper _{2,

3} , Bradley T. Hyman ₂ , Eva-Maria Mandelkow _{3,

4} , Eckhard Mandelkow _{3,

4} , Daniel J. Müller ₁

Affiliation

Misfolding and aggregation of the neuronal, microtubule-associated protein tau is involved in the pathogenesis of Alzheimer’s disease and tauopathies. It has been proposed that neuronal membranes could play a role in tau release, internalization, and aggregation and that tau aggregates could exert toxicity via membrane permeabilization. Whether and how tau interacts with lipid membranes remains a matter of discussion. Here, we characterize the interaction of full-length human tau (htau40) with supported lipid membranes (SLMs) made from brain total lipid extract by time-lapse high-resolution atomic force microscopy (AFM). We observe that tau attaches to brain lipid membranes where it self-assembles in a cation-dependent manner. Sodium triggers the attachment, self-assembly, and growth, whereas potassium inhibits these processes. Moreover, tau assemblies are stable in the presence of sodium and lithium but disassemble in the presence of potassium and rubidium. Whereas the pseudorepeat domains (R1–R4) of htau40 promote the sodium-dependent attachment to the membrane and stabilize the tau assemblies, the N-terminal region promotes tau self-assembly and growth.

中文翻译：

人头在支持的脑脂质膜上的可逆阳离子选择性附着和自组装。

神经元，微管相关蛋白tau的错误折叠和聚集与阿尔茨海默氏病和陶氏病的发病机理有关。已经提出，神经元膜可以在tau释放，内在化和聚集中起作用，并且tau聚集体可以通过膜透化发挥毒性。tau是否与脂质膜相互作用以及如何与脂质膜相互作用仍是讨论的问题。在这里，我们通过延时高分辨率高分辨率原子力显微镜（AFM）表征全长人tau（htau40）与由脑总脂质提取物制成的支持脂质膜（SLM）的相互作用。我们观察到，tau附着在脑脂质膜上，在那里它以阳离子依赖的方式自组装。钠触发附着，自组装和生长，而钾抑制这些过程。而且，tau组件在钠和锂的存在下是稳定的，但在钾和rub的存在下会分解。htau40的假重复结构域（R1-R4）促进了钠依赖性膜的附着并稳定了tau组件，而N末端区域则促进了tau的自组装和生长。

更新日期：2018-04-12

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