Nine unanswered questions about cytokinesis

Pollard, Thomas D.

doi:10.1083/jcb.201612068

Cited by 77 publications

(73 citation statements)

References 105 publications

(173 reference statements)

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“…Except the fact that we employ an elastic rather than a viscous cortex, our setup resembles the situation of cell cytokinesis [16,17,[19][20][21]. Cell cytokinesis as part of cell division is a prominent subject of active matter research in biological physics [13,18,97]. Most previous studies, e.g.…”

Section: Model Application: Cell Division In Suspending Fluidmentioning

confidence: 99%

Computational modeling of active deformable membranes embedded in three-dimensional flows

Bächer

Gekle

2019

Phys. Rev. E

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Active gel theory has recently been very successful in describing biologically active materials such as actin filaments or moving bacteria in temporally fixed and simple geometries such as cubes or spheres. Here we develop a computational algorithm to compute the dynamic evolution of an arbitrarily shaped, deformable thin membrane of active material embedded in a 3D flowing liquid. For this, our algorithm combines active gel theory with the classical theory of thin elastic shells. To compute the actual forces resulting from active stresses, we apply a parabolic fitting procedure to the triangulated membrane surface. Active forces are then dynamically coupled via an Immersed-Boundary method to the surrounding fluid whose dynamics can be solved by any standard, e.g. Lattice-Boltzmann, flow solver. We validate our algorithm using the Green's functions of [Berthoumieux et al. New J. Phys. 16, 065005 (2014)] for an active cylindrical membrane subjected (i) to a locally increased active stress and (ii) to a homogeneous active stress. For the latter scenario, we predict in addition a so far unobserved non-axisymmetric instability. We highlight the versatility of our method by analyzing the flow field inside an actively deforming cell embedded in external shear flow. Further applications may be cytoplasmic streaming or active membranes in blood flows. Published as: Phys. Rev. E 99(6), 062418 (2019)

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Section: Model Application: Cell Division In Suspending Fluidmentioning

confidence: 99%

Computational modeling of active deformable membranes embedded in three-dimensional flows

Bächer

Gekle

2019

Phys. Rev. E

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“…Our work demonstrates that crosstalk between microtubules and the furrow machinery mediated by Rho is conserved more broadly than previously thought and raises many intriguing questions regarding the molecular details of this communication in fungal cells. During cytokinesis of metazoan cells, RhoA regulates the location of the cytokinetic ring, activates formins for cytokinetic ring assembly, promotes myosin activity through Rho-associated protein kinase (ROCK), and promotes midbody ring maturation through Citron kinase (Pollard, 2017;El-Amine et al, 2019). Ring positioning is achieved through other mechanisms in fission yeast (Pollard, 2017), but Rho1 contributes to full activation of the SIN to drive ring formation (Alcaide-Gavilán et al, 2014) and has essential roles in septum synthesis through its interaction with glucan synthases (Arellano et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…During cytokinesis of metazoan cells, RhoA regulates the location of the cytokinetic ring, activates formins for cytokinetic ring assembly, promotes myosin activity through Rho-associated protein kinase (ROCK), and promotes midbody ring maturation through Citron kinase (Pollard, 2017;El-Amine et al, 2019). Ring positioning is achieved through other mechanisms in fission yeast (Pollard, 2017), but Rho1 contributes to full activation of the SIN to drive ring formation (Alcaide-Gavilán et al, 2014) and has essential roles in septum synthesis through its interaction with glucan synthases (Arellano et al, 1996). This suggests that Rho signaling is an ancient mechanism for coordinating cytoskeletal elements and that during the divergence from the LECA (the last eukaryote common ancestor) Rho signaling has been adapted for a range of functions to regulate cytokinesis.…”

Section: Discussionmentioning

confidence: 99%

Microtubule Nucleation Promoters Mto1 and Mto2 Regulate Cytokinesis in Fission Yeast

Dundon

Pollard

2019

Preprint

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Dundon and Pollard show that compromising the Mto1 or Mto2 regulators of the fission yeast γtubulin complex reduces or eliminates astral microtubules, exaggerates the effects of a non-lethal D277N substitution in β-glucan synthase 1 (Cps1/Bgs1) on the rate of cytokinetic furrow formation, and increases Rho-GTP at the cleavage site. AbstractMicrotubules of the mitotic spindle direct cytokinesis in metazoans but this has not been documented in fungi. We report evidence that astral microtubules help coordinate cytokinetic furrow formation in fission yeast. The temperature-sensitive cps1-191 strain (Liu et al., 1999) with a D277N substitution in β-glucan synthase 1 (Cps1/Bgs1) was reported to arrest with an unconstricted contractile ring. We discovered that rings in cps1-191 cells do constrict slowly and that an S338N mutation in the mto2 gene is required with the bgs1 D277N mutation to reproduce the cps1-191 phenotype. Complexes of Mto2 and Mto1 with γ-tubulin regulate microtubule assembly. Deletion of Mto1 along with the bgs1 D277N mutation also gives the cps1-191 phenotype, which is not observed in mto2 S338N or mto1Δ cells expressing bgs1 + . Both mto2 S338N and mto1Δ cells nucleate fewer astral microtubules than normal and have higher levels of Rho1-GTP at the division site than wild-type cells. We report multiple conditions that sensitize mto1Δ and mto2 S338N cells to furrow ingression phenotypes. (159 words)

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“…The cell assembles an actomyosin ring that constricts simultaneously with septum deposition, leading to membrane ingression and furrow formation (Lee et al, 2012;Pollard, 2010). Substantial progress in our understanding of actomyosin ring assembly has been made, largely due to the plenary work by several groups using fission yeast as a model system (Johnson et al, 2012;Lee et al, 2012;Pollard, 2010;Pollard, 2017). Recent reports have also shed light on the mechanistic details of ring constriction in fission yeast (Stachowiak et al, 2014;Thiyagarajan et al, 2015;Zhou et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

The Cdc42 GEF, Gef1, promotes uniform protein distribution along the actomyosin ring to enable concentric furrowing

Onwubiko

Mlynarczyk

Wei

et al. 2018

Preprint

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Statement: (15-30 words): Gef1 and endocytic events at the assembled actomyosin ring facilitate uniform Cdc15 distribution along the ring thus enabling concentric furrow formation. ABSTRACTDuring cytokinesis, fission yeast coordinates actomyosin ring constriction with septum ingression, resulting in concentric furrow formation. Mechanisms coordinating septum ingression with the actomyosin ring remain unclear. We report that cells lacking the Cdc42 activator Gef1, combined with an activated allele of the formin, Cdc12, display non-concentric furrowing. Although cells that furrow non-concentrically display normal actomyosin rings, the scaffold Cdc15 is unevenly distributed along the ring. This suggests that after ring assembly, uniform Cdc15 distribution along the ring drives proper furrow formation. We find that Cdc15 levels at the ring are reduced in the activated cdc12 mutant, or upon disruption of Arp2/3 complex-dependent endocytic patches. Furthermore, Cdc15 levels in endocytic patches increase in gef1 mutants. We hypothesize that assembled rings recruit Cdc15 from endocytic patches. Patches with higher Cdc15 levels and slower ring-association rate lead to uneven Cdc15 distribution. Based on this hypothesis we developed a mathematical model that captures experimentally observed Cdc15 distributions along the ring. We propose that, at the ring, Gef1 and endocytic events promote uniform Cdc15 distribution to enable proper septum ingression and concentric furrow formation.

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Nine unanswered questions about cytokinesis

Abstract: Pollard provides an overview of open questions and future research directions for our understanding of cytokinesis.

Cited by 77 publications

References 105 publications

Computational modeling of active deformable membranes embedded in three-dimensional flows

Computational modeling of active deformable membranes embedded in three-dimensional flows

Microtubule Nucleation Promoters Mto1 and Mto2 Regulate Cytokinesis in Fission Yeast

The Cdc42 GEF, Gef1, promotes uniform protein distribution along the actomyosin ring to enable concentric furrowing

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