Human Fidgetin is a microtubule severing the enzyme and minus-end depolymerase that regulates mitosis.
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.
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA.
Suranjana
S
Mukherjee
J Daniel
JD
Diaz Valencia
Shannon
S
Stewman
Jeremy
J
Metz
Sylvain
S
Monnier
Uttama
U
Rath
Ana B
AB
Asenjo
Rabab A
RA
Charafeddine
Hernando J
HJ
Sosa
Jennifer L
JL
Ross
Ao
A
Ma
David J
DJ
Sharp
D000074183:ATPases Associated with Diverse Cellular Activities / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000705:Anaphase; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014404:Tubulin; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C000613810:FIGN protein, human