Human fidgetin is a microtubule severing enzyme and minus-end depolymerase that regulates mitosis

Suranjana Mukherjee, J. Daniel Diaz Valencia, Shannon Stewman, Jeremy Metz, Sylvain Monnier, Uttama Rath, Ana B. Asenjo, Rabab A. Charafeddine, Hernando J. Sosa, Jennifer L. Ross, Ao Ma, David J. Sharp

Research output: Contribution to journalArticle

35 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)2359-2366
Number of pages8
JournalCell Cycle
Volume11
Issue number12
DOIs
StatePublished - Jun 15 2012
Externally publishedYes

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Keywords

  • Centrosome
  • Fidgetin
  • Microtubule severing enzymes
  • Microtubule-minus end depolymerase
  • Mitosis
  • Spindle

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Mukherjee, S., Diaz Valencia, J. D., Stewman, S., Metz, J., Monnier, S., Rath, U., Asenjo, A. B., Charafeddine, R. A., Sosa, H. J., Ross, J. L., Ma, A., & Sharp, D. J. (2012). Human fidgetin is a microtubule severing enzyme and minus-end depolymerase that regulates mitosis. Cell Cycle, 11(12), 2359-2366. https://doi.org/10.4161/cc.20849