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Characterization of Ring-Like F-Actin Structure as a Mechanical Partner for Spindle Positioning in Mitosis

机译:像环一样的F-肌动蛋白结构作为有丝分裂中主轴定位的机械伙伴的表征

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摘要

Proper spindle positioning and orientation are essential for accurate mitosis which requires dynamic interactions between microtubule and actin filament (F-actin). Although mounting evidence demonstrates the role of F-actin in cortical cytoskeleton dynamics, it remains elusive as to the structure and function of F-actin-based networks in spindle geometry. Here we showed a ring-like F-actin structure surrounding the mitotic spindle which forms since metaphase and maintains in MG132-arrested metaphase HeLa cells. This cytoplasmic F-actin structure is relatively isotropic and less dynamic. Our computational modeling of spindle position process suggests a possible mechanism by which the ring-like F-actin structure can regulate astral microtubule dynamics and thus mitotic spindle orientation. We further demonstrated that inhibiting Plk1, Mps1 or Myosin, and disruption of microtubules or F-actin polymerization perturbs the formation of the ring-like F-actin structure and alters spindle position and symmetric division. These findings reveal a previously unrecognized but important link between mitotic spindle and ring-like F-actin network in accurate mitosis and enables the development of a method to theoretically illustrate the relationship between mitotic spindle and cytoplasmic F-actin.
机译:正确的纺锤定位和方向对于准确的有丝分裂至关重要,而有丝分裂需要微管和肌动蛋白丝(F-肌动蛋白)之间发生动态相互作用。尽管越来越多的证据表明F-肌动蛋白在皮质细胞骨架动力学中的作用,但对于纺锤体几何中基于F-肌动蛋白的网络的结构和功能仍然难以捉摸。在这里,我们显示了围绕有丝分裂纺锤体的环状F-肌动蛋白结构,该结构自中期形成并在MG132停滞的中期HeLa细胞中维持。这种胞质F-肌动蛋白结构相对各向同性,动态性较低。我们的纺锤体定位过程的计算模型提出了一种可能的机制,通过该机制,环状F-肌动蛋白结构可以调节星状微管动力学,从而调节有丝分裂纺锤体的定向。我们进一步证明,抑制Plk1,Mps1或肌球蛋白,以及破坏微管或F-肌动蛋白聚合会扰乱环状F-肌动蛋白结构的形成,并改变纺锤体的位置和对称分裂。这些发现揭示了有丝分裂纺锤体和环状F-肌动蛋白网络之间在精确的有丝分裂中以前未被认识但重要的联系,并使理论上阐明有丝分裂纺锤体和细胞质F-肌动蛋白之间关系的方法得以发展。

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