Abstract

The primary goal of cytokinesis is to produce two daughter cells, each having a full set of chromosomes. To achieve this, cells assemble a dynamic structure between segregated sister chromatids called the contractile ring, which is made up of filamentous actin, myosin-II, and other regulatory proteins. Constriction of the actomyosin ring generates a cleavage furrow that divides the cytoplasm to produce two daughter cells. Decades of research have identified key regulators and underlying molecular mechanisms; however, many fundamental questions remain unanswered and are still being actively investigated. This review summarizes the key findings, computational modeling, and recent advances in understanding of the molecular mechanisms that control the formation of the cleavage furrow and cytokinesis.

Highlights

  • Cytokinesis, the last step of cell division, physically divides the cytoplasm by forming an actomyosin contractile ring between the segregated chromosomes; thereby ensuring that each daughter cell receives a full set of chromosomes

  • In addition to chromosomal passenger complex (CPC) and the centralspindlin complex, many key regulatory proteins, such as Polo like kinase 1 (PLK1), Protein Regulator of Cytokinesis 1 (PRC1), and the Rho GTPase Guanine nucleotide-exchange factor (GEF) ECT2, accumulate at the central spindle, which led to the proposal that the midzone microtubules provide a platform from which critical signaling cues for cleavage furrow specification originate

  • In Drosophila S2 cells, we recently showed that many key regulators of cytokinesis localize to and track MT plus-ends [62]

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Summary

Introduction

Cytokinesis, the last step of cell division, physically divides the cytoplasm by forming an actomyosin contractile ring between the segregated chromosomes; thereby ensuring that each daughter cell receives a full set of chromosomes. Spatial and temporal control of cleavage furrow formation between daughter nuclei is crucial for preserving the ploidy of a cell [1]. Failure in cleavage furrow formation and cytokinesis can give rise to tetraploid cells, which can further lead to aneuploidy. A cell must ensure spatiotemporal positioning, maintenance, and completion of the cleavage furrow with high fidelity. We review different models that have been proposed to describe the mechanisms by which cells establish the cleavage plane, provide an overview of the key regulators that control spatiotemporal patterning of RhoA, discuss the utility of computational modeling, summarize our recent knowledge of propagating waves in cytokinesis and highlight some of the outstanding questions

Classical Models of Cytokinesis
Central Spindle Stimulation Model
Astral Stimulation Model
Classical
Polar Relaxation Model
Spatiotemporal Regulation of Cytokinetic Events
Aurora Kinases
Rho GTPases in Cytokinesis
Computational Modeling of Cytokinesis
What Specifies the Site of the Furrow?
How Does the Contractile Ring Assemble?
How Does the Ring Generate Force?
How Does this Force Form the Furrow?
Midzone-Independent Signaling in Cleavage Plane Specification
Astral Stimulation and Polar Relaxation
Propagating Waves of Contractility in Cytokinesis
10. Summary and Outlook
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