Abnormal Tau phosphorylation of the Alzheimer-type also occurs during mitosis.
In Alzheimer's disease, neurofibrillary degeneration results from the aggregation of abnormally phosphorylated Tau proteins into filaments and it may be related to the reactivation of mitotic mechanisms. In order to investigate the link between Tau phosphorylation and mitosis, Xenopus laevis oocytes in which most of the M-phase regulators have been discovered were used as a cell model. The human Tau isoform htau412 (2+3-10+) was microinjected into prophase I oocytes that were then stimulated by progesterone that activate cyclin-dependent kinase pathways. Hyperphosphorylation of the Tau isoform, which is characterized by a decrease of its electrophoretic mobility and its labelling by a number of phosphorylation-dependent antibodies, was observed at the time of germinal vesicle breakdown. Surprisingly, Tau immunoreactivity, considered as typical of Alzheimer's pathology (AT100 and phospho-Ser422), was observed in meiosis II. Because meiosis II is considered as a mitosis-like phase, we investigated if our observation was also relevant to a neurone-like model. Abnormal Tau phosphorylation was detected in mitotic human neuroblastoma SY5Y cells overexpressing Tau. Regarding AT100-immunoreactivity and phospho-Ser422, we suggest that phosphatase 2A inhibition and a phosphorylation combination of mitotic kinases may lead to this Alzheimer-type phosphorylation. Our results not only demonstrate the involvement of mitotic kinases in Alzheimer-type Tau phosphorylation but also indicate that Xenopus oocyte could be a useful model to identify the kinases involved in this process.
Delobel
Patrice
P
INSERM U422, Institut de Médecine Prédictive et Recherche Thérapeutique, Lille, France.
Flament
Stéphane
S
Hamdane
Malika
M
Mailliot
Christel
C
Sambo
Anne-Véronique
AV
Bégard
Séverine
S
Sergeant
Nicolas
N
Delacourte
André
A
Vilain
Jean-Pierre
JP
Buée
Luc
L
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000939:Epitopes / Q000502:physiology; D006801:Humans; D008540:Meiosis / Q000502:physiology; D008845:Microinjections; D008938:Mitosis / Q000502:physiology*; D009447:Neuroblastoma / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D014162:Transfection; D014981:Xenopus; D016875:tau Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*
D000939:Epitopes; D016875:tau Proteins; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2