Tunneling Nanotubes (TNTs): Structure, Formation and Role in Neurodegenerative Diseases Spreading

− この都医学研セミナーは終了しました。 −

演者 Chiara Zurzolo
Pasteur Institute, Paris, France (Head of Department)
会場 東京都医学総合研究所 2階 BC会議室
日時 平成29年9月11日(月)15:00~
世話人 野中 隆(認知症・高次脳機能研究分野 認知症プロジェクト)
参加自由 詳細は下記問合せ先まで
お問い合わせ 研究推進課 普及広報係
電話 03-5316-3109


Neurodegenerative diseases (NDs) like Prion disease, Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s (HD) disease are part of a larger group of protein misfolding disorders characterized by the progressive accumulation and spreading of different protein aggregates. Like Prions, misfolded forms of ASYN, tau, Abeta and Htt proteins associated with AD, PD and HD can be transmitted experimentally in cellular and in animal models where act as ‘seeds’ to recruit the endogenous protein into aggregates. However, the mechanism of intercellular transfer is still debated. We have recently described a novel mechanism of PrPSc transmission through Tunneling Nanotubes (TNTs)1. TNTs are actin-based protrusions connecting cells in culture and represents a novel mechanism of cell-to-cell communication. Furthermore mutant polyQ Htt aggregates appear to highjack TNTs2 as well as fibrillar and oligomeric ASYN assemblies3 and Tau fibrils4. We propose that TNTs contribute to the progression of the pathology of NDs by spreading in the brain of misfolded protein assemblies5. We also demonstrated that in vitro and in ex vivo culture models astrocytes have a role in degrading asyn fibrils rather then in transfer6.

Thus, understanding the mechanism of TNT formation is important to uncover their physiological function. We demonstrate that despite their similarities, filopodia and TNTs form through distinct molecular mechanisms7 indicating that they are different structures. Finally, analysis by correlative cryo-EM and tomography (Sartori, et al. under revision) show differences in the actin organization and appearance of the two structures revealing their unique identities.

  1. Gousset et al, NCB 2009
  2. Costanzo et al, JCS 2013
  3. Abounit et al, EMBO J 2016
  4. Abounit et al, Prion 2016
  5. Victoria and Zurzolo, JCB 2017
  6. Loria et al, Acta Neuropathol 2017
  7. Delage et al, Sci Rep 2016