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

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.