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 Citations (Scopus)

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

Fingerprint

Mitosis
Microtubules
Centrosome
Enzymes
Anaphase
Spindle Apparatus
Chromatids
Tubulin
Paclitaxel
Small Interfering RNA
Growth
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Mukherjee, S., Diaz Valencia, J. D., Stewman, S., Metz, J., Monnier, S., Rath, U., ... 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

Human fidgetin is a microtubule severing enzyme and minus-end depolymerase that regulates mitosis. / Mukherjee, Suranjana; Diaz Valencia, J. Daniel; Stewman, Shannon; Metz, Jeremy; Monnier, Sylvain; Rath, Uttama; Asenjo, Ana B.; Charafeddine, Rabab A.; Sosa, Hernando J.; Ross, Jennifer L.; Ma, Ao; Sharp, David J.

In: Cell Cycle, Vol. 11, No. 12, 15.06.2012, p. 2359-2366.

Research output: Contribution to journalArticle

Mukherjee, S, Diaz Valencia, JD, Stewman, S, Metz, J, Monnier, S, Rath, U, Asenjo, AB, Charafeddine, RA, Sosa, HJ, Ross, JL, Ma, A & Sharp, DJ 2012, 'Human fidgetin is a microtubule severing enzyme and minus-end depolymerase that regulates mitosis', Cell Cycle, vol. 11, no. 12, pp. 2359-2366. https://doi.org/10.4161/cc.20849
Mukherjee S, Diaz Valencia JD, Stewman S, Metz J, Monnier S, Rath U et al. Human fidgetin is a microtubule severing enzyme and minus-end depolymerase that regulates mitosis. Cell Cycle. 2012 Jun 15;11(12):2359-2366. https://doi.org/10.4161/cc.20849
Mukherjee, Suranjana ; Diaz Valencia, J. Daniel ; Stewman, Shannon ; Metz, Jeremy ; Monnier, Sylvain ; Rath, Uttama ; Asenjo, Ana B. ; Charafeddine, Rabab A. ; Sosa, Hernando J. ; Ross, Jennifer L. ; Ma, Ao ; Sharp, David J. / Human fidgetin is a microtubule severing enzyme and minus-end depolymerase that regulates mitosis. In: Cell Cycle. 2012 ; Vol. 11, No. 12. pp. 2359-2366.
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