Pathological tau phenotypes. The weight of mutations, polymorphisms, and differential neuronal vulnerabilities.
In tauopathies, comparative biochemistry of tau aggregates shows that they differ in both phosphorylation and content of tau isoforms. Six tau isoforms are found in human brain that contain either three (3R) or four microtubule-binding domains (4R). In Alzheimer's disease, all six of the tau isoforms are phosphorylated and aggregate into paired helical filaments. They are detected by immunoblotting as a major tau triplet (tau 55, 64, and 69). In corticobasal degeneration and progressive supranuclear palsy, only phosphorylated 4R-tau isoforms aggregate and appear as a major tau doublet (tau 64 and 69). In Pick's disease, only phosphorylated 3R-tau isoforms aggregate into filaments and are characterized by another major tau doublet (tau 55 and 64). Finally, recent findings provide a direct link between a genetic defect in tau and its abnormal aggregation into filaments in frontotemporal dementia with parkinsonism linked to chromosome 17. In the present study, the question of a relationship between tau isoforms and cell morphology is raised. To answer this question, stably transfected human neuroblastoma SY5Y cell lines with either 3R- or 4R-tau isoforms are established. Cell morphology and tau phosphorylation were modified, suggesting that cells undergo profound changes in their metabolism and viability.
Mailliot
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INSERM U422, Place de Verdun, F-59045 Lille Cedex, France.
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Hamdane
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Sergeant
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Caillet
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Delacourte
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Buée
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D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002886:Chromosomes, Human, Pair 17; D006801:Humans; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D010766:Phosphorylation; D020774:Pick Disease of the Brain / Q000235:genetics / Q000473:pathology; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics; D013494:Supranuclear Palsy, Progressive / Q000235:genetics / Q000473:pathology; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics*
D020033:Protein Isoforms; D016875:tau Proteins