Microtubule-severing enzymes: From cellular functions to molecular mechanism

J Cell Biol. 2018 Dec 3;217(12):4057-4069. doi: 10.1083/jcb.201612104. Epub 2018 Oct 29.

Abstract

Microtubule-severing enzymes generate internal breaks in microtubules. They are conserved in eukaryotes from ciliates to mammals, and their function is important in diverse cellular processes ranging from cilia biogenesis to cell division, phototropism, and neurogenesis. Their mutation leads to neurodegenerative and neurodevelopmental disorders in humans. All three known microtubule-severing enzymes, katanin, spastin, and fidgetin, are members of the meiotic subfamily of AAA ATPases that also includes VPS4, which disassembles ESCRTIII polymers. Despite their conservation and importance to cell physiology, the cellular and molecular mechanisms of action of microtubule-severing enzymes are not well understood. Here we review a subset of cellular processes that require microtubule-severing enzymes as well as recent advances in understanding their structure, biophysical mechanism, and regulation.

Publication types

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

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Animals
  • Class III Phosphatidylinositol 3-Kinases / metabolism*
  • Humans
  • Katanin / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / enzymology*
  • Spastin / metabolism*

Substances

  • Microtubule-Associated Proteins
  • Class III Phosphatidylinositol 3-Kinases
  • ATPases Associated with Diverse Cellular Activities
  • FIGN protein, human
  • Spastin
  • Katanin
  • SPAST protein, human

Associated data

  • PDB/3B9P
  • PDB/5WC1
  • PDB/2RPA
  • PDB/5NBT
  • PDB/3EAB
  • PDB/5WC0
  • PDB/5WCB