Role of the Tau N-terminal region in microtubule stabilization revealed by newendogenous truncated forms

• DOI: 10.1038/srep09659
• Publication Date: 2015-05-14T15:36:18Z
• Authors: Maxime Derisbourg; Coline Leghay; Giovanni Chiappetta; Francisco-Jose Fe...; Cyril Laurent; Dominique Demeyer; Sébastien Carrier; Valérie Buée-Sche...; David Blum; Joëlle Vinh; Nicolas Sergeant; Yann Verdier; Luc Buée; Malika Hamdane
• Keywords: Proteomics; 0303 health sciences; [SDV]Life Sciences [q-bio]; Brain; Acetylation; tau Proteins; Microtubules; Article; Cell Line; [SDV] Life Sciences [q-bio]; 03 medical and health sciences; Alzheimer Disease; Tubulin; Nerve Degeneration; [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology; Humans; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology; [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Phosphorylation; Protein Processing, Post-Translational; Protein Binding

AbstractTau is a central player in Alzheimer's disease (AD) and relatedTauopathies, where it is found as aggregates in degenerating neurons. Abnormalpost-translational modifications, such as truncation, are likely involved in thepathological process. A major step forward in understanding the role of Tautruncation would be to identify the precise cleavage sites of the several truncatedTau fragments that are observed until now in AD brains, especially those truncatedat the N-terminus, which are less characterized than those truncated at theC-terminus. Here, we optimized a proteomics approach and succeeded in identifying anumber of new N-terminally truncated Tau species from the human brain. We initiatedcell-based functional studies by analyzing the biochemical characteristics of twoN-terminally truncated Tau species starting at residues Met11 and Gln124respectively. Our results show, interestingly, that the Gln124-Tau fragment displaysa stronger ability to bind and stabilize microtubules, suggesting that the TauN-terminal domain could play a direct role in the regulation of microtubulestabilization. Future studies based on our new N-terminally truncated-Tau speciesshould improve our knowledge of the role of truncation in Tau biology as well as inthe AD pathological process.