Human Fidgetin Is a Microtubule Severing the Enzyme and Minus-End Depolymerase That Regulates Mitosis

Cell Cycle. 2012 Jun 15;11(12):2359-66. doi: 10.4161/cc.20849. Epub 2012 Jun 15.

Abstract

Fidgetin is a member of the AAA protein superfamily with important roles in mammalian development. Here we show that human Fidgetin is a potent microtubule severing and depolymerizing the enzyme used to regulate mitotic spindle architecture, dynamics and anaphase A. In vitro, recombinant human Fidgetin severs taxol-stabilized microtubules along their length and promotes depolymerization, primarily from their minus-ends. In cells, human Fidgetin targets to centrosomes, and its depletion with siRNA significantly reduces the velocity of poleward tubulin flux and anaphase A chromatid-to-pole motion. In addition, the loss of Fidgetin induces a microtubule-dependent enlargement of mitotic centrosomes and an increase in the number and length of astral microtubules. Based on these data, we propose that human Fidgetin actively suppresses microtubule growth from and attachment to centrosomes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / antagonists & inhibitors
  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Anaphase
  • Cell Line, Tumor
  • Centrosome / metabolism
  • Humans
  • Microtubule-Associated Proteins / antagonists & inhibitors
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Mitosis*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spindle Apparatus / metabolism
  • Tubulin / metabolism

Substances

  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • Tubulin
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities
  • FIGN protein, human