Aurora B‐dependent polarization of the cortical actomyosin network during mitotic exit

Ramkumar, Nitya; Patel, Jigna V.; Anstatt, Jannis; Baum, Buzz

doi:10.15252/embr.202152387

Cited by 11 publications

(9 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In mammalian cells, Aurora A may function in parallel to Cdk1 ( Su et al, 2011 ) to antagonize cortical association of Ect2 at certain times of the cell cycle. A recent report, relying primarily on chemical inhibitors of Aurora kinases, indicates that Aurora B promotes clearance of F-actin from the polar cortex ( Ramkumar et al, 2021 ). However, these inhibitors are not highly selective for Aurora A vs. Aurora B at the concentrations used in cell-based assays ( de Groot et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…This is well characterized in C. elegans embryos where the centralspindlin-dependent and -independent furrows have been separated genetically ( Dechant and Glotzer, 2003 ; Werner et al, 2007 ). Analogous phenomena operate in cultured human cells ( Chen et al, 2021 ; Murthy and Wadsworth, 2008 ; Ramkumar et al, 2021 ; Rodrigues et al, 2015 ). In early C. elegans embryos, centralspindlin functions in parallel with NOP-1 to promote ECT-2-dependent RHO-1 activation ( Morton et al, 2012 ; Tse et al, 2012 ; Fievet et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation

Longhini

Glotzer

2022

eLife

View full text Add to dashboard Cite

In the early C. elegans embryo, cell polarization and cytokinesis are interrelated yet distinct processes. Here, we sought to understand a poorly understood aspect of cleavage furrow positioning. Early C. elegans embryos deficient in the cytokinetic regulator centralspindlin form furrows, due to an inhibitory activity that depends on aster positioning relative to the polar cortices. Here, we show polar relaxation is associated with depletion of cortical ECT-2, a RhoGEF, specifically at the posterior cortex. Asymmetric ECT-2 accumulation requires intact centrosomes, Aurora A (AIR-1), and myosin-dependent cortical flows. Within a localization competent ECT-2 fragment, we identified three putative phospho-acceptor sites in the PH domain of ECT-2 that render ECT-2 responsive to inhibition by AIR-1. During both polarization and cytokinesis, our results suggest that centrosomal AIR-1 breaks symmetry via ECT-2 phosphorylation; this local inhibition of ECT-2 is amplified by myosin-driven flows that generate regional ECT-2 asymmetry. Together, these mechanisms cooperate to induce polarized assembly of cortical myosin, contributing to both embryo polarization and cytokinesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation

Longhini

Glotzer

2022

eLife

View full text Add to dashboard Cite

show abstract

“…In mammalian cells, Aurora A may function in parallel to Cdk1 (Su et al, 2011) to antagonize membrane association of Ect2 at certain times of the cell cycle. A recent report, relying primarily on chemical inhibitors of Aurora kinases, indicates Aurora B promotes clearance of f-actin from the polar cortex (Ramkumar et al, 2021). However, these inhibitors are not highly selective for Aurora A vs Aurora B at the concentrations used in cell-based assays (de Groot et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…This is well characterized in C. elegans embryos where the centralspindlin-dependent and -independent furrows have been separated genetically (Dechant and Glotzer, 2003; Werner et al, 2007). Analogous phenomena operate in cultured human cells (Murthy and Wadsworth, 2008; Rodrigues et al, 2015; Chen et al, 2021; Ramkumar et al, 2021). In early C. elegans embryos, centralspindlin functions in parallel with NOP-1 to promote ECT-2-dependent RHO-1 activation (Fievet et al, 2012; Morton et al, 2012; Tse et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation

Longhini-Aldis

Glotzer

2022

Preprint

View full text Add to dashboard Cite

In the early C. elegans embryo, cell polarization and cytokinesis are interrelated yet distinct processes. Here, we sought to understand a poorly understood aspect of cleavage furrow positioning. Early C. elegans embryos deficient in the cytokinetic regulator centralspindlin form furrows, due to an inhibitory activity that depends on aster positioning relative to the polar cortex. Polar relaxation is associated with depletion of the cortical RhoGEF, ECT-2, specifically at the posterior pole. Asymmetric ECT-2 accumulation requires intact centrosomes, Aurora A (AIR-1), and myosin-dependent cortical flows. Within a localization competent ECT-2 fragment, we identified three putative phospho-acceptor sites in the PH domain of ECT-2 that render ECT-2 responsive to inhibition by AIR-1. AIR-1 and cortical flows cooperate to promote embryo polarization. During both polarization and cytokinesis, centrosomal AIR-1 breaks symmetry via ECT-2 phosphorylation; this local inhibition of ECT-2 is amplified by myosin-driven flows that generate regional ECT-2 asymmetry. Together, these mechanisms cooperate to induce polarized assembly of cortical myosin, contributing to both embryo polarization and cytokinesis.

show abstract

“…The chromosomal phenotypes induced by shortening or lengthening spindle assembly duration highlight the importance of not only controlling spindle size but also the kinetics of assembly. Affecting the duration of spindle assembly might also alter the temporal coordination between chromosome segregation and other cellular events such as spindle and cell division orientation [ 146 , 147 ], polarity establishment [ 148 ], cortical actomyosin organization [ 149 , 150 ] and cytokinetic furrow ingression [ 151 ]. Such perturbations would be detrimental for cell cycle progression and development.…”

Section: Physiological Relevance Of Spindle Scaling: a Matter Of Size And/or Time?mentioning

confidence: 99%

Spatial and Temporal Scaling of Microtubules and Mitotic Spindles

Lacroix

Dumont

2022

Cells

View full text Add to dashboard Cite

During cell division, the mitotic spindle, a macromolecular structure primarily comprised of microtubules, drives chromosome alignment and partitioning between daughter cells. Mitotic spindles can sense cellular dimensions in order to adapt their length and mass to cell size. This scaling capacity is particularly remarkable during early embryo cleavage when cells divide rapidly in the absence of cell growth, thus leading to a reduction of cell volume at each division. Although mitotic spindle size scaling can occur over an order of magnitude in early embryos, in many species the duration of mitosis is relatively short, constant throughout early development and independent of cell size. Therefore, a key challenge for cells during embryo cleavage is not only to assemble a spindle of proper size, but also to do it in an appropriate time window which is compatible with embryo development. How spatial and temporal scaling of the mitotic spindle is achieved and coordinated with the duration of mitosis remains elusive. In this review, we will focus on the mechanisms that support mitotic spindle spatial and temporal scaling over a wide range of cell sizes and cellular contexts. We will present current models and propose alternative mechanisms allowing cells to spatially and temporally coordinate microtubule and mitotic spindle assembly.

show abstract

Aurora B‐dependent polarization of the cortical actomyosin network during mitotic exit

Cited by 11 publications

References 54 publications

Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation

Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation

Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation

Spatial and Temporal Scaling of Microtubules and Mitotic Spindles

Contact Info

Product

Resources

About