1. Human Fidgetin is a microtubule severing the enzyme and minus-end depolymerase that regulates mitosis
- Author
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Jeremy Metz, Shannon F. Stewman, J. Daniel Diaz Valencia, Rabab A. Charafeddine, Hernando J. Sosa, Uttama Rath, Jennifer L. Ross, Sylvain Monnier, Ao Ma, David J. Sharp, Suranjana Mukherjee, and Ana B. Asenjo
- Subjects
macromolecular substances ,Cell Biology ,Biology ,Cell biology ,Spindle apparatus ,Tubulin ,Microtubule ,Centrosome ,biology.protein ,Astral microtubules ,Molecular Biology ,Mitosis ,Developmental Biology ,Anaphase ,Microtubule severing - 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.
- Published
- 2012
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