title: N-terminal truncation of microtubule associated protein tau dysregulates its cellular localization.
abstract: Tau protein is a member of microtubule-associated protein family. Under pathological conditions, tau undergoes multiple modifications that lead to the formation of insoluble deposits in neurons, resulting in neuronal dysfunction in several neurodegenerative disorders collectively called tauopathies, with Alzheimer's disease being the most frequent example. This typical cytosolic protein has been shown to translocate into the nucleus and participate in DNA protection upon stress conditions. In our study, we demonstrate that truncated Tau151-391/4R changes its usual behavior and gains constitutive access into the nucleus of both primary rat neurons and human neuroblastoma cells. Our results show that partial/dysregulated nuclear localization of tau results from the removal of the N-terminal (1-150) residues of the protein. Data obtained by cell fractionation data were supported by confocal microscopy analysis of GFP-fused tau proteins. Furthermore, neither addition of the fusion protein, nor increased tau phosphorylation had any effect on the intracellular distribution of truncated tau. Our data further suggest that differential tau phospho-status between cytosolic and nuclear fractions is rather a consequence than a cause of truncated tau nuclear localization. Finally, truncated tau in the nucleus is engaged in interactions with subnuclear structure(s), since it exhibits reduced mobility. We conclude that N-terminal truncation of tau proteins leads to their nonphysiological subcellular distribution as a result of modified tau conformation.
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Kristina
authors.initials: K
authors.lastname: Paholikova
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Barbara
authors.initials: B
authors.lastname: Salingova
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Opattova
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic AXON Neuroscience SE, Bratislava, Slovak Republic.
authors.forename: Rostislav
authors.initials: R
authors.lastname: Skrabana
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Majerova
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic AXON Neuroscience SE, Bratislava, Slovak Republic.
authors.forename: Norbert
authors.initials: N
authors.lastname: Zilka
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic AXON Neuroscience SE, Bratislava, Slovak Republic.
authors.forename: Branislav
authors.initials: B
authors.lastname: Kovacech
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic AXON Neuroscience SE, Bratislava, Slovak Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Zilkova
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic AXON Neuroscience SE, Bratislava, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Barath
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic AXON Neuroscience SE, Bratislava, Slovak Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D013347:Subcellular Fractions; D024801:Tauopathies / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: Alzheimer's disease; cell compartmentation; cell nucleus; neurodegenerative diseases; tau proteins; truncation