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Detection and Quantification of Tunneling Nanotubes Using 3D Volume View Images
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Published on: August 31, 2022

Prions hijack tunnelling nanotubes for intercellular spread.

Karine Gousset1, Edwin Schiff, Christelle Langevin

  • 1Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.

Nature Cell Biology
|February 10, 2009
PubMed
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Tunnelling nanotubes (TNTs) facilitate the spread of prions (PrP(Sc)) between neuronal cells and from dendritic cells to neurons. This discovery reveals TNTs as a key pathway for prion disease progression.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Prion Disease Research

Background:

  • Variant Creutzfeldt-Jakob disease involves prions (PrP(Sc)) spreading from the gut to the central nervous system (CNS).
  • The precise mechanism of cell-to-cell prion spread, particularly to the CNS, remains unclear.
  • Tunnelling nanotubes (TNTs) are known intercellular structures facilitating cell-to-cell communication.

Purpose of the Study:

  • To investigate the role of tunnelling nanotubes (TNTs) in the intercellular spread of prions (PrP(Sc)).
  • To determine if TNTs mediate prion transfer between neuronal cells and from immune cells to neurons.

Main Methods:

  • Co-culturing infected and naive neuronal CAD cells connected by TNTs.
  • Observing the transfer of exogenous and endogenous PrP(Sc) using microscopy.
  • Analyzing PrP(Sc) transfer from bone marrow-derived dendritic cells to primary neurons via TNTs.

Main Results:

  • Tunnelling nanotubes (TNTs) were shown to enable the transfer of both exogenous and endogenous prions (PrP(Sc)) between neuronal CAD cells.
  • Endogenous PrP(Sc) aggregate transfer was specifically observed in infected cells connected by TNTs, confirming TNTs' role in neuronal prion spread.
  • Labeled PrP(Sc) transfer from dendritic cells to neurons was detected through TNTs, suggesting a neuroimmune pathway for prion dissemination.

Conclusions:

  • Tunnelling nanotubes (TNTs) represent an efficient route for prion (PrP(Sc)) spreading within neuronal cells.
  • TNTs mediate prion transfer from peripheral sites, involving dendritic cells and neurons, potentially facilitating retrograde transport to the CNS.
  • The findings implicate TNTs in the neuroimmune transmission of prions from the periphery to the central nervous system.