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tau N 端基序在 End Binding 蛋白介导的人 tau 分泌中的作用。

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

机构信息

Centre for Biomedical Research of the Canary Islands (CIBICAN), Institute for Biomedical Technologies (ITB), University of La Laguna (ULL), Tenerife, Spain.

Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain, CIEN Foundation, Queen Sofia Foundation Alzheimer Center, Madrid, Spain.

出版信息

PLoS One. 2019 Jan 22;14(1):e0210864. doi: 10.1371/journal.pone.0210864. eCollection 2019.

DOI:10.1371/journal.pone.0210864
PMID:30668577
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6342323/
Abstract

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.

摘要

由于未知的原因,人类似乎特别容易发生导致神经退行性变的 tau 病理学变化。转基因小鼠无疑仍然是研究阿尔茨海默病和其他 tau 病的最受欢迎和广泛使用的动物模型。虽然这些鼠模型通常在小鼠大脑或特定脑区过度表达人类 tau,但内源性小鼠 tau 和人类 tau 蛋白之间存在差异。其中,人类 tau 和小鼠 tau 之间的主要区别之一是人类 tau 蛋白中存在一个短序列,跨越残基 18 到 28,而在小鼠 tau 中缺失,这至少部分导致了不同物种之间的易感性差异。在这里,我们报告了使用亲和层析分析的新数据,表明包含人类 tau 残基 18 到 28 的序列充当 End Binding 蛋白的结合基序,并且这种相互作用可以促进 tau 向细胞外空间的分泌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/d6541a8be7ca/pone.0210864.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/738a8e158876/pone.0210864.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/98c0fb4c6059/pone.0210864.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/6abbd893d967/pone.0210864.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/9c72be3fb22c/pone.0210864.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/d6541a8be7ca/pone.0210864.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/738a8e158876/pone.0210864.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/98c0fb4c6059/pone.0210864.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/6abbd893d967/pone.0210864.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/9c72be3fb22c/pone.0210864.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba2e/6342323/d6541a8be7ca/pone.0210864.g005.jpg

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