Ectosomes: a new mechanism for non-exosomal secretion of tau protein

PLoS One. 2014 Jun 27;9(6):e100760. doi: 10.1371/journal.pone.0100760. eCollection 2014.

Abstract

Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as tauopathies. Recently, studies have suggested that Tau may be secreted and play a role in neural network signalling. However, once deregulated, secreted Tau may also participate in the spreading of Tau pathology in hierarchical pathways of neurodegeneration. The mechanisms underlying neuron-to-neuron Tau transfer are still unknown; given the known role of extra-cellular vesicles in cell-to-cell communication, we wondered whether these vesicles could carry secreted Tau. We found, among vesicles, that Tau is predominately secreted in ectosomes, which are plasma membrane-originating vesicles, and when it accumulates, the exosomal pathway is activated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell-Derived Microparticles / metabolism*
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Exosomes / metabolism
  • Extracellular Fluid / metabolism
  • Humans
  • Microscopy, Electron
  • Neurons / cytology
  • Neurons / metabolism
  • Rats
  • Rats, Wistar
  • tau Proteins / metabolism*

Substances

  • tau Proteins

Grants and funding

This work was supported through the LabEx DISTALZ (an excellent laboratory- Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's disease), the FUI MEDIALZ and CPER DN2M (VICTAUR), Inserm, CNRS, University of Lille 2, Lille Métropole Communauté Urbaine (LMCU), Région Nord/Pas-de-Calais, FEDER and the ‘Fondation Plan Alzheimer’ (PRIMATAU). We thank the IMPRT (Lille) for access to core facilities (animal housing, D. Taillieu; EM, C. Allet). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.