Lu Huan, Zhao Qun, Jiang Hao, Zhu Tongge, Xia Peng, Seffens William, Aikhionbare Felix, Wang Dongmei, Dou Zhen, Yao Xuebiao
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui, China.
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui, China; Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia, United States of America.
PLoS One. 2014 Oct 9;9(10):e102547. doi: 10.1371/journal.pone.0102547. eCollection 2014.
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.
正确的纺锤体定位和定向对于精确的有丝分裂至关重要，而这需要微管与肌动蛋白丝（F-肌动蛋白）之间的动态相互作用。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发挥作用，但F-肌动蛋白网络在纺锤体几何形状中的结构和功能仍不清楚。在这里，我们展示了一种围绕有丝分裂纺锤体的环状F-肌动蛋白结构，该结构从中期开始形成，并在MG132阻断的中期HeLa细胞中维持。这种细胞质F-肌动蛋白结构相对各向同性且动态性较低。我们对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，并改变纺锤体位置和对称分裂。这些发现揭示了在精确的有丝分裂中，有丝分裂纺锤体与环状F-肌动蛋白网络之间以前未被认识但很重要的联系，并使得能够开发一种从理论上说明有丝分裂纺锤体与细胞质F-肌动蛋白之间关系的方法。
