title: Evidence of a balance between phosphorylation and O-GlcNAc glycosylation of Tau proteins--a role in nuclear localization.
abstract: Both phosphorylation and O-GlcNAc glycosylation posttranslationally modify microtubule-associated Tau proteins. Whereas the hyperphosphorylation of these proteins that occurs in Alzheimer's disease is well characterized, little is known about the O-GlcNAc glycosylation. The present study demonstrates that a balance exists between phosphorylation and O-GlcNAc glycosylation of Tau proteins, and furthermore that a dysfunction of this balance correlates with reduced nuclear localization. The affinity of Tau proteins for WGA lectin, together with evidence from [3H]-galactose transfer and analysis of beta-eliminated products, demonstrated the presence of O-GlcNAc residues on both cytosolic and nuclear Tau proteins. In addition, our data indicated the existence of a balance between phosphorylation and O-GlcNAc glycosylation events. Indeed, as demonstrated by 2D-electrophoresis and Western blotting, O-GlcNAc residues were mainly located on the less phosphorylated Tau 441 variants, whereas the more phosphorylated forms were devoid of O-GlcNAc residues. Furthermore, the Tau protein hyperphosphorylation induced by cellular okadaic acid treatment was correlated with reduced incorporation of O-GlcNAc residues into Tau proteins and with diminished Tau transfer into the nucleus. Hence, this paper establishes a direct relationship between O-GlcNAc glycosylation, phosphorylation and cellular localization of Tau proteins.
authors.affiliation: Laboratoire de Chimie Biologique, Unité Mixte de Recherches 8576 du CNRS, Université des Sciences et Technologies de Lille I, F-59655 Villeneuve d'Ascq, France.
authors.forename: Tony
authors.initials: T
authors.lastname: Lefebvre
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ferreira
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dupont-Wallois
authors.forename: Thierry
authors.initials: T
authors.lastname: Bussière
authors.forename: Marie-Joëlle
authors.initials: MJ
authors.lastname: Dupire
authors.forename: André
authors.initials: A
authors.lastname: Delacourte
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Caillet-Boudin
mesh_terms: D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D016875:tau Proteins; D019319:Okadaic Acid; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase