RESUMEN
The main difference between the primary structures of human and mouse tau can be found at the N-terminal end of the protein. Residues 17 to 28 in human tau are not present in the mouse form of the molecule. Here we tested the capacity of these human tau residues to bind to specific proteins. Several proteins were observed to bind to these residues. Among those that showed the greatest binding were three related to energetic processes: enolase, glyceraldehyde 3 phosphate dehydrogenase and creatine kinase B. The latter did not bind to tau from brain extracts taken from patients with Alzheimer's disease (AD). This lack of binding could be due to the modification of CKB by oxidation in AD.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Proteínas tau/química , Proteínas tau/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Animales , Sitios de Unión , Forma BB de la Creatina-Quinasa/metabolismo , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Fosfopiruvato Hidratasa/metabolismo , Unión Proteica , Ratas , Alineación de SecuenciaRESUMEN
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.