Nuclear tau, a key player in neuronal DNA protection.
Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease, which is primarily described as a microtubule-associated protein, has also been observed in the nuclei of neuronal and non-neuronal cells. However, the function of the nuclear form of Tau in neurons has not yet been elucidated. In this work, we demonstrate that acute oxidative stress and mild heat stress (HS) induce the accumulation of dephosphorylated Tau in neuronal nuclei. Using chromatin immunoprecipitation assays, we demonstrate that the capacity of endogenous Tau to interact with neuronal DNA increased following HS. Comet assays performed on both wild-type and Tau-deficient neuronal cultures showed that Tau fully protected neuronal genomic DNA against HS-induced damage. Interestingly, HS-induced DNA damage observed in Tau-deficient cells was completely rescued after the overexpression of human Tau targeted to the nucleus. These results highlight a novel role for nuclear Tau as a key player in early stress response.
Inserm UMR837, Alzheimer and Tauopathies, 1 rue Michel Polonovski, 59045 Lille, France.
Audrey
A
Sultan
Fabrice
F
Nesslany
Marie
M
Violet
Séverine
S
Bégard
Anne
A
Loyens
Smail
S
Talahari
Zeyni
Z
Mansuroglu
Daniel
D
Marzin
Nicolas
N
Sergeant
Sandrine
S
Humez
Morvane
M
Colin
Eliette
E
Bonnefoy
Luc
L
Buée
Marie-Christine
MC
Galas
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
C054369:MAPT protein, human; D016875:tau Proteins; D004247:DNA