Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA.
Cell Cycle. 2012 Jun 15;11(12):2359-66. doi: 10.4161/cc.20849.
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.
Fidgetin 是 AAA 蛋白超家族的成员，在哺乳动物发育中具有重要作用。在这里，我们表明人类 Fidgetin 是一种有效的微管切割酶和去聚合酶，用于调节有丝分裂纺锤体结构、动力学和后期 A。在体外，重组人 Fidgetin 沿着紫杉醇稳定的微管的长度进行切割，并促进解聚，主要从微管的负端开始。在细胞中，人 Fidgetin 靶向中心体，其 siRNA 耗竭显著降低了极向微管流和后期 A 染色单体向极的运动速度。此外，Fidgetin 的缺失诱导有丝分裂中心体的微管依赖性增大，以及星状微管数量和长度的增加。基于这些数据，我们提出人类 Fidgetin 积极抑制微管从中心体生长和附着。
