Tau secretion is correlated to an increase of Golgi dynamics

PLoS One. 2017 May 26;12(5):e0178288. doi: 10.1371/journal.pone.0178288. eCollection 2017.

Abstract

Tau protein can be released by neurons, an event linked to the propagation of Tau pathology in Alzheimer'disease (AD). Neuronal hyperexcitability was shown to significantly increase Tau release by neurons. We confirmed this in the present study. In a previous study, it was demonstrated that hyperexcitability induces Golgi apparatus dynamics resulting in its fragmentation. Our present results revealed that the increase of Tau secretion upon hyperexcitability could be significantly reduced by preventing Golgi dynamics through the inactivation of cdk5. We then verified whether a Golgi fragmentation not induced by hyperexcitability could also increase Tau secretion. The suppression of Rab1A, Rab GTPase associated with the Golgi membranes, known to induce a Golgi fragmentation increased Tau secretion by both neurons and HeLa cells. Although it remains to be demonstrated whether the Golgi is directly involved in Tau secretion, the present results demonstrate that its dynamics are correlated to a modulation of Tau secretion.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Cyclin-Dependent Kinase 5 / metabolism
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • tau Proteins / metabolism*

Substances

  • tau Proteins
  • Cyclin-Dependent Kinase 5
  • CDK5 protein, human

Grants and funding

This work was supported by a grant from the Canadian Institute of Health Research [MOP-114874 to NL], and an FRQS infrastructure grant to the Groupe de Recherche sur le système nerveux central (GRSNC) to NL. N-VM. has a studentship from the GRSNC and the Faculté des Études Supérieures et Post-Doctorales of University of Montréal (FESP).