Tau overexpression impairs neuronal endocytosis by decreasing the GTPase dynamin 1 through the miR-132/MeCP2 pathway

Aging Cell. 2019 Jun;18(3):e12929. doi: 10.1111/acel.12929. Epub 2019 Feb 27.

Abstract

Tauopathies are a class of neurodegenerative diseases that are characterized by pathological aggregation of tau protein, which is accompanied by synaptic disorders. However, the role of tau in endocytosis, a fundamental process in synaptic transmission, remains elusive. Here, we report that forced expression of human tau (hTau) in mouse cortical neurons impairs endocytosis by decreasing the level of the GTPase dynamin 1 via disruption of the miR-132-MeCP2 pathway; this process can also be detected in the brains of Alzheimer's patients and hTau mice. Our results provide evidence for a novel role of tau in the regulation of presynaptic function.

Keywords: Tau; dynamin 1; endocytosis; miR-132.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Animals
  • Dynamin I / metabolism*
  • Endocytosis* / genetics
  • Humans
  • Methyl-CpG-Binding Protein 2 / metabolism*
  • Mice
  • MicroRNAs / metabolism*
  • Neurons / metabolism*
  • tau Proteins / genetics*
  • tau Proteins / metabolism

Substances

  • MIRN132 microRNA, mouse
  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • MicroRNAs
  • tau Proteins
  • Dynamin I