Inhibition of polar actin assembly by astral microtubules is required for cytokinesis

Anan Chen,Darren A Yuen,Trevor F Moraes,Thomas C Panagiotou,Andrew Wilde,Brigitte D Lavoie,Luisa Ulloa Severino

doi:10.1038/s41467-021-22677-0

Anan Chen, Darren A Yuen + Show 5 more

Open Access

https://doi.org/10.1038/s41467-021-22677-0

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Abstract

During cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. Here we demonstrate that the opposing regulation of the β- and γ-actin networks is required for successful cytokinesis. While activation of the formin DIAPH3 at the cytokinetic furrow underlies β-actin filament production, we show that the γ-actin network is specifically depleted at the cell poles through the localized deactivation of the formin DIAPH1. During anaphase, CLIP170 is delivered by astral microtubules and displaces IQGAP1 from DIAPH1, leading to formin autoinhibition, a decrease in cortical stiffness and localized membrane blebbing. The contemporaneous production of a β-actin contractile ring at the cell equator and loss of γ-actin from the poles is required to generate a stable cytokinetic furrow and for the completion of cell division.

Highlights

During cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex
DIAPH3 is recruited to the cytokinetic furrow as the cell exits metaphase by the scaffolding protein anillin, and requires activation through the binding of both RhoA and anillin to release it from its autoinhibited state[9]
As the chromosomes segregate during anaphase A, and prior to furrow ingression, β and γ-actin begin to asymmetrically redistribute around the cortex such that β-actin becomes enriched at the site of future furrow ingression at the cell equator

Summary

Introduction

The actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. The contemporaneous production of a β-actin contractile ring at the cell equator and loss of γ-actin from the poles is required to generate a stable cytokinetic furrow and for the completion of cell division. As each complete copy of the genetic material is segregated to the opposite poles of the cell, a furrow of plasma membrane, the cytokinetic furrow, ingresses between them fusing and generating two new cells. To alleviate any pressure imbalance during anaphase, small membranous extrusions, termed blebs, form at the cell poles[13] These and other observations demonstrate that events at the poles of the cell are important for successful cytokinesis[11,15,16]

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