Severing enzymes amplify microtubule arrays through lattice GTP-tubulin incorporation

Science. 2018 Aug 24;361(6404):eaau1504. doi: 10.1126/science.aau1504.

Abstract

Spastin and katanin sever and destabilize microtubules. Paradoxically, despite their destructive activity they increase microtubule mass in vivo. We combined single-molecule total internal reflection fluorescence microscopy and electron microscopy to show that the elemental step in microtubule severing is the generation of nanoscale damage throughout the microtubule by active extraction of tubulin heterodimers. These damage sites are repaired spontaneously by guanosine triphosphate (GTP)-tubulin incorporation, which rejuvenates and stabilizes the microtubule shaft. Consequently, spastin and katanin increase microtubule rescue rates. Furthermore, newly severed ends emerge with a high density of GTP-tubulin that protects them against depolymerization. The stabilization of the newly severed plus ends and the higher rescue frequency synergize to amplify microtubule number and mass. Thus, severing enzymes regulate microtubule architecture and dynamics by promoting GTP-tubulin incorporation within the microtubule shaft.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Drosophila melanogaster
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Katanin / metabolism*
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Microtubules / metabolism*
  • Microtubules / ultrastructure*
  • Single Molecule Imaging
  • Spastin / metabolism*
  • Tubulin / metabolism*

Substances

  • Tubulin
  • Guanosine Triphosphate
  • Spastin
  • Katanin