Role of tau N-terminal motif in the secretion of human tau by End Binding proteins

For unknown reasons, humans appear to be particular susceptible to developing tau pathology leading to neurodegeneration. Transgenic mice are still undoubtedly the most popular and extensively used animal models for studying Alzheimer’s disease and other tauopathies. While these murine models generally overexpress human tau in the mouse brain or specific brain regions, there are differences between endogenous mouse tau and human tau protein. Among them, a main difference between human and mouse tau is the presence of a short motif spanning residues 18 to 28 in the human tau protein that is missing in murine tau, and which could be at least partially responsible for that different susceptibility across species. Here we report novel data using affinity chromatography analysis indicating that the sequence containing human tau residues 18 to 28 acts a binding motif for End Binding proteins and that this interaction could facilitate tau secretion to the extracellular space.出于未知原因，人类似乎尤其易患引发神经退行性病变的tau蛋白病（tau pathology）。毋庸置疑，转基因小鼠仍是目前研究阿尔茨海默病（Alzheimer’s disease）及其他tau蛋白病（tauopathies）最常用且被广泛应用的动物模型。尽管这类小鼠模型通常会在小鼠大脑或特定脑区过表达人源tau蛋白，但内源性小鼠tau蛋白与人源tau蛋白之间存在显著差异。其中，人与小鼠tau蛋白的一个核心差异在于：人源tau蛋白存在一段跨度为18至28号氨基酸残基的短基序（motif），而小鼠tau蛋白中缺失该序列，这一差异可能至少部分解释了不同物种间的易感性差异。本研究通过亲和层析（affinity chromatography）分析获取了全新实验数据，结果显示：包含人源tau蛋白18至28号氨基酸残基的序列可作为End Binding蛋白（End Binding proteins）的结合基序，且二者的相互作用能够促进tau蛋白分泌至细胞外空间。