0 avis
Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms
Archive ouverte
Edité par CCSD ; Nature Publishing Group -
International audience. Tau is a central player in Alzheimer’s disease (AD) and related Tauopathies, where it is found as aggregatesin degenerating neurons. Abnormal post-translational modifications, such as truncation, are likely involvedin the pathological process. A major step forward in understanding the role of Tau truncation would be toidentify the precise cleavage sites of the several truncated Tau fragments that are observed until now in ADbrains, especially those truncated at the N-terminus, which are less characterized than those truncated at theC-terminus. Here, we optimized a proteomics approach and succeeded in identifying a number of newN-terminally truncated Tau species from the human brain. We initiated cell-based functional studies byanalyzing the biochemical characteristics of two N-terminally truncated Tau species starting at residuesMet11 and Gln124 respectively. Our results show, interestingly, that the Gln124-Tau fragment displays astronger ability to bind and stabilize microtubules, suggesting that the Tau N-terminal domain could play adirect role in the regulation of microtubule stabilization. Future studies based on our new N-terminallytruncated-Tau species should improve our knowledge of the role of truncation in Tau biology as well as inthe AD pathological process.
Consulter en ligne
Suggestions
Du même auteur
