Polar relaxation by dynein-mediated removal of cortical myosin II

Abstract

Nearly six decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction. While this mechanism has remained controversial, recent work has provided evidence for polar relaxation by astral microtubules, although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar relaxation is achieved through dynein-mediated removal of myosin II from the polar cortexes. Mutants that position centrosomes closer to the polar cortex accelerated furrow induction, whereas suppression of dynein activity delayed furrowing. We show that dynein-mediated removal of myosin II from the polar cortexes triggers a bidirectional cortical flow toward the cell equator, which induces the assembly of the actomyosin contractile ring. These results provide a molecular mechanism for the aster-dependent polar relaxation, which works in parallel with equatorial stimulation to promote robust cytokinesis.

Equatorial Non-muscle Myosin II and Plastin Cooperate to Align and Compact F-actin Bundles in the Cytokinetic Ring

“…Wolpert’s astral relaxation theory specifically proposed that a negative signal from the astral microtubules would make the poles relax, allowing the equator to contract ( Wolpert, 1960 ). While the molecular mechanisms for polar relaxation have only recently started to be unraveled ( Mangal et al, 2018 ; Chapa-y-lazo et al, 2020 ), it has become widely accepted that cytokinesis requires a positive signal from the central spindle that activates the small GTPase RhoA, which in turn promotes the accumulation of contractile ring components, F-actin and myosin, at the cell equator. F-actin alignment and accumulation via flow-driven equatorial compression and RhoA-dependent local recruitment are the two main mechanisms thought to drive the assembly of a circumferentially aligned contractile ring.…”

A flagellate-to-amoeboid switch in the closest living relatives of animals

“…Intracellular microtubule distribution regulates actomyosin activity in some animal cells ( Kopf et al, 2020 ; Chapa-y-Lazo et al, 2020 ) and in Dictyostelium ( Sugiyama et al, 2015 ), with microtubule-free zones experiencing higher local contractility and bleb retraction. In unconfined flagellated S. rosetta cells, we observed that cortical microtubules radiated from the apical basal body to form a cage underneath the entire plasma membrane, as previously reported ( Karpov and Leadbeater, 1998 ; Sebé-Pedrós et al, 2013a ; Figure 4—figure supplement 2A–D ).…”

Rac and Arp2/3-Nucleated Actin Networks Antagonize Rho During Mitotic and Meiotic Cleavages

“…There is now a general consensus that Rappaport’s “cleavage stimulus” involves the Chromosomal Passenger, PRC1/Kif4A, and centralspindlin complexes that organize the post-anaphase central spindle and direct the local activation of Rho ( Glotzer, 2009 ; Mishima, 2016 ; Basant and Glotzer, 2018 ). The notion of negative regulatory cues have a long history ( Wolpert, 1960 ) and there is evidence supporting the idea that there are antagonistic signals or mechanisms for clearing contractile proteins from the polar regions ( Murthy and Wadsworth, 2008 ; Kunda et al, 2012 ; Rodrigues et al, 2015 ; Mangal et al, 2018 ; Chapa-Y-Lazo et al, 2020 ). Rac has also been implicated as a negative regulator for cytokinesis ( D’Avino et al, 2004 ; Yoshizaki et al, 2004 ; Canman et al, 2008 ; Cannet et al, 2014 ), with proposed downstream effectors including PAK-mediated cell adhesion ( Bastos et al, 2012 ) and the Arp2/3 complex ( Canman et al, 2008 ).…”