Filamin-A and Myosin VI colocalize with fibrillary Tau protein in Alzheimer's disease and FTDP-17 brains.
Tauopathies, including Alzheimer's disease (AD), fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick's disease and progressive supranuclear palsy, are neurodegenerative disorders neuropathologically characterized by the presence of intraneuronal fibrillary inclusions composed of abnormally phosphorylated-Tau. Tau protein is a neuronal microtubule-associated protein (MAP) involved in microtubules polymerization and stabilization. So far, the molecular mechanisms underlying Tau-mediated cellular toxicity remain elusive. To address the determinants of Tau neurotoxicity, we previously performed a misexpression screening in a Drosophila tauopathy model to identify genetic modifiers of the human Tau-induced neurodegeneration. We identified several components of the actin network as modifiers of Tau V337M-induced neurodegeneration, i.e. Filamin-A, Myosin VI, Paxillin and Transgelin-3. The aim of this study was to assess whether these genetic interactions were associated with a colocalization of the proteins (i) in the brains of patients with Tau pathologies, and (ii) in the brain of transgenic mice overexpressing human mutant Tau. We found that Filamin-A and Myosin VI indeed colocalize with fibrillary Tau protein in AD and FTDP-17 and in Thy-Tau22 transgenic mice.
Feuillette
Sébastien
S
Inserm U614, Institute for Biomedical Research, Faculty of Medicine, University of Rouen, Rouen, France.
Deramecourt
Vincent
V
Laquerriere
Annie
A
Duyckaerts
Charles
C
Delisle
Marie-Bernadette
MB
Maurage
Claude-Alain
CA
Blum
David
D
Buée
Luc
L
Frébourg
Thierry
T
Campion
Dominique
D
Lecourtois
Magalie
M
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002886:Chromosomes, Human, Pair 17; D003285:Contractile Proteins / Q000378:metabolism*; D005260:Female; D064448:Filamins; D057180:Frontotemporal Dementia / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000378:metabolism; D020774:Pick Disease of the Brain / Q000378:metabolism; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism; D024801:Tauopathies / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D003285:Contractile Proteins; D064448:Filamins; C054369:MAPT protein, human; D008840:Microfilament Proteins; C089785:myosin VI; D016875:tau Proteins; D018995:Myosin Heavy Chains