Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms
Résumé
Tau is a central player in Alzheimer’s disease (AD) and related Tauopathies, where it is found as aggregates
in degenerating neurons. Abnormal post-translational modifications, such as truncation, are likely involved
in the pathological process. A major step forward in understanding the role of Tau truncation would be to
identify the precise cleavage sites of the several truncated Tau fragments that are observed until now in AD
brains, especially those truncated at the N-terminus, which are less characterized than those truncated at the
C-terminus. Here, we optimized a proteomics approach and succeeded in identifying a number of new
N-terminally truncated Tau species from the human brain. We initiated cell-based functional studies by
analyzing the biochemical characteristics of two N-terminally truncated Tau species starting at residues
Met11 and Gln124 respectively. Our results show, interestingly, that the Gln124-Tau fragment displays a
stronger ability to bind and stabilize microtubules, suggesting that the Tau N-terminal domain could play a
direct role in the regulation of microtubule stabilization. Future studies based on our new N-terminally
truncated-Tau species should improve our knowledge of the role of truncation in Tau biology as well as in
the AD pathological process.
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...