コンテンツへスキップ
Merck
  • The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system.

The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system.

Nature communications (2023-02-03)
Itika Saha, Patricia Yuste-Checa, Miguel Da Silva Padilha, Qiang Guo, Roman Körner, Hauke Holthusen, Victoria A Trinkaus, Irina Dudanova, Rubén Fernández-Busnadiego, Wolfgang Baumeister, David W Sanders, Saurabh Gautam, Marc I Diamond, F Ulrich Hartl, Mark S Hipp
要旨

Amyloid-like aggregates of the microtubule-associated protein Tau are associated with several neurodegenerative disorders including Alzheimer's disease. The existence of cellular machinery for the removal of such aggregates has remained unclear, as specialized disaggregase chaperones are thought to be absent in mammalian cells. Here we show in cell culture and in neurons that the hexameric ATPase valosin-containing protein (VCP) is recruited to ubiquitylated Tau fibrils, resulting in their efficient disaggregation. Aggregate clearance depends on the functional cooperation of VCP with heat shock 70 kDa protein (Hsp70) and the ubiquitin-proteasome machinery. While inhibition of VCP activity stabilizes large Tau aggregates, disaggregation by VCP generates seeding-active Tau species as byproduct. These findings identify VCP as a core component of the machinery for the removal of neurodegenerative disease aggregates and suggest that its activity can be associated with enhanced aggregate spreading in tauopathies.

材料
製品番号
ブランド
製品内容

Roche
抗GFP, from mouse IgG1κ (clones 7.1 and 13.1)
Sigma-Aldrich
抗グリセルアルデヒド-3-リン酸デヒドロゲナーゼ抗体、クローン6C5, clone 6C5, Chemicon®, from mouse
Sigma-Aldrich
抗α-チューブリン抗体, マウスモノクローナル, clone DM1A, purified from hybridoma cell culture
Sigma-Aldrich
抗LC3B ウサギ宿主抗体, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
抗マウスIgG (全分子)-ペルオキシダーゼ ヤギ宿主抗体, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
抗ユビキチン化タンパク質抗体、クローンFK2, clone FK2, Upstate®, from mouse
Sigma-Aldrich
抗ウサギIgG (全分子)-ペルオキシダーゼ ヤギ宿主抗体, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
抗ユビキチン抗体、Lys63-特異的、クローンApu3、ウサギモノクローナル, clone Apu3, from rabbit
Sigma-Aldrich
Anti-Ubiquitin Antibody, Lys48-Specific, clone Apu2, rabbit monoclonal, clone Apu2, from rabbit
Sigma-Aldrich
抗NPLOC4抗体 ウサギ宿主抗体, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, Ab1