The role of the VQIVYK peptide in tau protein phosphorylation.
Although it remains unclear whether they are related to one another, tau aggregation and phosphorylation are the main pathological hallmarks of the neuronal disorders known as tauopathies. The capacity to aggregate is impaired in a variant of the tau 3R isoform that lacks residues 306-311 (nomenclature for the largest CNS tau isoform) and hence, we have taken advantage of this feature to study how phosphorylation and aggregation may be related as well as the role of this six amino acid peptide (VQIVYK). Through these analyses, we found that the phosphorylation of the tau variant was higher than that of the complete tau protein and that not only the deletion of these residues, but also the interaction of these residues, in tau 3R, with thioflavin-S augmented tau phosphorylation by glycogen synthase kinase 3. In addition, the binding of the peptide containing the residues 306-311 to the whole tau protein provoked an increase in tau phosphorylation. This observation could be physiologically relevant as may suggest that tau-tau interactions, through those residues, facilitate tau phosphorylation. In summary, our data indicate that deletion of residues VQIVYK, in tau protein produces an increase in tau phosphorylation, without tau aggregation, because the VQIVYK peptide, that favors aggregation, is missing. On the other hand, when the whole tau protein interacts with thioflavin-S or the peptide VQIVYK, an increase in both aggregation and phosphorylation occurs.
Centro de Biología Molecular "Severo Ochoa" CSIC/UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Mar
M
Perez
Ismael
I
Santa-María
Elena
E
Tortosa
Raquel
R
Cuadros
Mercedes
M
Del Valle
Felix
F
Hernández
Francisco J
FJ
Moreno
Jesús
J
Avila
D000818:Animals; D052160:Benzothiazoles; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D017384:Sequence Deletion; D013844:Thiazoles / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D052160:Benzothiazoles; D010446:Peptide Fragments; D013844:Thiazoles; D016875:tau Proteins; C009462:thioflavin T