The potential role of tau protein O-glycosylation in Alzheimer's disease.
Single O-linked N-acetylglucosamine (O-GlcNAc) sugar residues can compete with phosphate groups to occupy specific sites on certain nuclear and cytosolic proteins. Here we show that inhibiting cellular kinase activities resulted in changes in protein O-glycosylation levels in heat-stable cytoskeletal protein fractions derived from primary neuronal cells. As increased phosphorylation of the microtubule-associated protein tau is one of the pathological hallmarks of Alzheimer's disease and glycosylation may play an influential role in this process. We observed a significant decrease in the protein O-GlcNAc glycosylation of a tau-enriched cytoskeletal fraction generated from AD post-mortem brain samples as compared with control, suggesting an inverse relationship between the two post-translational modifications. Finally, cells transfected with the cDNA coding for O-GlcNAc transferase (OGT) displayed altered tau phosphorylation patterns as compared with control cells, suggesting that changes in tau glycosylation may influence its phosphorylation state. The specificity of the changes in the phosphorylation of individual amino acid residues provides evidence for a targeted O-glycosylation of tau.
Robertson
Laura A
LA
Alzheimer's Disease Research Centre, Division of Pathology and Neuroscience, University of Dundee Medical School, Ninewells Hospital, Dundee DD1 9SY, UK.
Moya
Kenneth L
KL
Breen
Kieran C
KC
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D003704:Dementia / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D012680:Sensitivity and Specificity; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins
C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D016875:tau Proteins