Microtubules gate tau condensation to spatially regulate microtubule functions

Nat Cell Biol. 2019 Sep;21(9):1078-1085. doi: 10.1038/s41556-019-0375-5. Epub 2019 Sep 2.

Abstract

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Mice
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Neuroimaging / methods
  • Neurons / metabolism
  • Spastin / metabolism*
  • Swine
  • tau Proteins / metabolism*

Substances

  • Microtubule-Associated Proteins
  • tau Proteins
  • Spastin