Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies

Acta Neuropathol Commun. 2016 Nov 4;4(1):117. doi: 10.1186/s40478-016-0386-4.

Abstract

A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer's disease, is a bona fide constituent of TNTs. This is important because Tau appears beside filamentous actin and myosin 10 as a specific marker of these fine protrusions of membranes and cytosol that are difficult to visualize. Furthermore, we observed that exogenous Tau species increase the number of TNTs established between primary neurons, thereby facilitating the intercellular transfer of Tau fibrils. In conclusion, Tau may contribute to the formation and function of the highly dynamic TNTs that may be involved in the prion-like propagation of Tau assemblies.

Publication types

  • Video-Audio Media
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Biological Transport / physiology
  • Cell Communication*
  • Cell Line
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / ultrastructure
  • Extracellular Space / metabolism
  • Genetic Vectors
  • Humans
  • Lentivirus / genetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Myosins / metabolism
  • Neurons / metabolism*
  • Neurons / ultrastructure*
  • Rats, Wistar
  • Tubulin / genetics
  • Tubulin / metabolism
  • tau Proteins / genetics
  • tau Proteins / metabolism*

Substances

  • Actins
  • Luminescent Proteins
  • MAPT protein, human
  • Myo10 protein, mouse
  • Tubulin
  • myosin X, rat
  • tau Proteins
  • Myosins