title: Two-dimensional electrophoresis of tau mutants reveals specific phosphorylation pattern likely linked to early tau conformational changes.
abstract: The role of Tau phosphorylation in neurofibrillary degeneration linked to Alzheimer's disease remains to be established. While transgenic mice based on FTDP-17 Tau mutations recapitulate hallmarks of neurofibrillary degeneration, cell models could be helpful for exploratory studies on molecular mechanisms underlying Tau pathology. Here, "human neuronal cell lines" overexpressing Wild Type or mutated Tau were established. Two-dimensional electrophoresis highlights that mutated Tau displayed a specific phosphorylation pattern, which occurs in parallel to the formation of Tau clusters as visualized by electron microscopy. In fact, this pattern is also displayed before Tau pathology onset in a well established mouse model relevant to Tau aggregation in Alzheimer's disease. This study suggests first that pathological Tau mutations may change the distribution of phosphate groups. Secondly, it is possible that this molecular event could be one of the first Tau modifications in the neurofibrillary degenerative process, as this phenomenon appears prior to Tau pathology in an in vivo model and is linked to early steps of Tau nucleation in Tau mutants cell lines. Such cell lines consist in suitable and evolving models to investigate additional factors involved in molecular pathways leading to whole Tau aggregation.
authors.affiliation: Inserm, U837, Place de Verdun, Lille, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bretteville
authors.forename: Kunie
authors.initials: K
authors.lastname: Ando
authors.forename: Antoine
authors.initials: A
authors.lastname: Ghestem
authors.forename: Anne
authors.initials: A
authors.lastname: Loyens
authors.forename: Séverine
authors.initials: S
authors.lastname: Bégard
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Beauvillain
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdane
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009154:Mutation; D010766:Phosphorylation; D011487:Protein Conformation; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins