Abstract

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.

Highlights

  • For the past decades, our understanding on molecular components, assembly and function of mitotic spindle has achieved great advance [1]

  • Identification of a ring-like F-actin structure during mitosis It is generally believed that mitotic spindle governs chromosome partitioning and segregation in eukaryotes

  • As the cell goes through metaphase, F-actin staining becomes apparent around the entire spindle (Fig. 1A; b, arrow)

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Summary

Introduction

Our understanding on molecular components, assembly and function of mitotic spindle has achieved great advance [1]. Comparing the biochemical mechanism of mitotic spindle, the biophysical mechanism, especially a mechanical force chain stretching across the mitotic cell, remains elusive. This force chain starts in the region of extracellular substrate-cell cortex fringe with adhesion proteins and actin filaments [2,3,4,5]. The pulling and pushing force on spindle microtubules is regulated by motor proteins and mitotic signals [14,15,16,17] This part is involved in the spindle assembly checkpoint (SAC), which precludes anaphase entry until all chromosomes achieve biorientation [18,19,20]

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