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Dr. Chiara Zurzolo - Tunneling nanotubes: structure, formation and role in the progression of neurodegenerative diseases

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Chiara Zurzolo

Institut Pasteur, Unité de Trafic membranaire et Pathogenèse, Paris

Tunneling nanotubes (TNTs): structure, formation and role in the progression of neurodegenerative diseases

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.  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 mechanisms6 indicating that they are different structures. Finally, analysis by correlative cryo-EM and tomography (Sartori, et al. in preparation) show differences in the actin organization and appearance of the two structures revealing their unique identities.

 

References

1 Gousset et al. Nat Cell Biol 2009 

2 Costanzo et al. J Cell Sci 2013

3 Abounit et al. EMBO J 2016

4 Abounit et al. Prion 2016

5 Victoria and Zurzolo J Cell Biol 2017

6 Delage et al. Sci Rep 2016

 

Contact: Isabelle Maridonneau-Parini (isabelle.maridonneau-parini@ipbs.fr)

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23 Jan

11:00 - 12:00

Seminar room - IPBS - Campus 205