title: Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms.
abstract: 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.
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Derisbourg
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: Coline
authors.initials: C
authors.lastname: Leghay
authors.affiliation: ESPCI Biological Mass Spectrometry and Proteomics USR 3149 CNRS/ESPCI ParisTech, Paris, France.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Chiappetta
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France.
authors.forename: Francisco-Jose
authors.initials: FJ
authors.lastname: Fernandez-Gomez
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Laurent
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Demeyer
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Carrier
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Buée-Scherrer
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.affiliation: ESPCI Biological Mass Spectrometry and Proteomics USR 3149 CNRS/ESPCI ParisTech, Paris, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Vinh
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.affiliation: ESPCI Biological Mass Spectrometry and Proteomics USR 3149 CNRS/ESPCI ParisTech, Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Verdier
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: 1] Inserm, UMR-S 1172, Alzheimer &Tauopathies, Jean-Pierre Aubert Research Centre, Faculté de Médecine, IMPRT, F-59045, Lille, France [2] Université de Lille, F-59045, Lille, France [3] CHRU-Lille, F-59037, Lille, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdane
mesh_terms: D000107:Acetylation; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000473:pathology; D002460:Cell Line; D006801:Humans; D008870:Microtubules / Q000502:physiology*; D009410:Nerve Degeneration / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D014404:Tubulin / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D014404:Tubulin; D016875:tau Proteins