Fronts and waves of actin polymerization in a bistability-based mechanism of circular dorsal ruffles

Bernitt, Erik; Döbereiner, Jürgen; Gov, Nir S.; Yochelis, Arik

doi:10.1038/ncomms15863

Cited by 44 publications

(64 citation statements)

References 54 publications

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“…Moreover, our analysis demonstrates that wave dynamics need to be appropriately balanced between bistable and excitable regimes (reflected in the choice of model parameter b) to reproduce the pinch-off behavior observed in our experiments. Note that bistability was also identified as a key element in describing the dynamics of circular dorsal ruffles, actin-based ring-shaped precursors of macropinocytic cups (46). We believe that a phenomenological modeling approach that identifies the minimal dynamical features needed to recover the experimental observations will be particularly beneficial for guiding future efforts to reconstitute primitive cytofission scenarios in synthetic systems.…”

Section: Discussionmentioning

confidence: 95%

How cortical waves drive fission of motile cells

Flemming

Font

Alonso

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Cytokinesis—the division of a cell into two daughter cells—is a key step in cell growth and proliferation. It typically occurs in synchrony with the cell cycle to ensure that a complete copy of the genetic information is passed on to the next generation of daughter cells. In animal cells, cytokinesis commonly relies on an actomyosin contractile ring that drives equatorial furrowing and separation into the two daughter cells. However, also contractile ring-independent forms of cell division are known that depend on substrate-mediated traction forces. Here, we report evidence of an as yet unknown type of contractile ring-independent cytokinesis that we termed wave-mediated cytofission. It is driven by self-organized cortical actin waves that travel across the ventral membrane of oversized, multinucleatedDictyostelium discoideumcells. Upon collision with the cell border, waves may initiate the formation of protrusions that elongate and eventually pinch off to form separate daughter cells. They are composed of a stable elongated wave segment that is enclosed by a cell membrane and moves in a highly persistent fashion. We rationalize our observations based on a noisy excitable reaction–diffusion model in combination with a dynamic phase field to account for the cell shape and demonstrate that daughter cells emerging from wave-mediated cytofission exhibit a well-controlled size.

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Section: Discussionmentioning

confidence: 95%

How cortical waves drive fission of motile cells

Flemming

Font

Alonso

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Merlin lacks the ERM actin-binding domain but can interact with α-catenin, an actin-binding protein that influences Arp2/3-driven actin branching (Drees et al 2005;Gladden et al 2010). Differences in cortical actin configuration and membrane:actin cross-linking could dramatically impact the formation and amplification of actin waves that underlie the dorsal and peripheral ruffles that initiate macropinocytosis via the differential recruitment of actin modifiers or modulation of membrane tension; those differences also impact receptor mobility and the diffusion of signals emanating from an activated receptor (Clayton and Cousin 2009;Gauthier et al 2012;Kusumi et al 2012;Bernitt et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Merlin/ERM proteins regulate growth factor-induced macropinocytosis and receptor recycling by organizing the plasma membrane:cytoskeleton interface

et al. 2018

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The architectural and biochemical features of the plasma membrane are governed by its intimate association with the underlying cortical cytoskeleton. The neurofibromatosis type 2 (NF2) tumor suppressor merlin and closely related membrane:cytoskeleton-linking protein ezrin organize the membrane:cytoskeleton interface, a critical cellular compartment that both regulates and is regulated by growth factor receptors. An example of this poorly understood interrelationship is macropinocytosis, an ancient process of nutrient uptake and membrane remodeling that can both be triggered by growth factors and manage receptor availability. We show that merlin deficiency primes the membrane:cytoskeleton interface for epidermal growth factor (EGF)-induced macropinocytosis via a mechanism involving increased cortical ezrin, altered actomyosin, and stabilized cholesterol-rich membranes. These changes profoundly alter EGF receptor (EGFR) trafficking in merlin-deficient cells, favoring increased membrane levels of its heterodimerization partner, ErbB2; clathrin-independent internalization; and recycling. Our work suggests that, unlike Ras transformed cells, merlin-deficient cells do not depend on macropinocytic protein scavenging and instead exploit macropinocytosis for receptor recycling. Finally, we provide evidence that the macropinocytic proficiency of NF2-deficient cells can be used for therapeutic uptake. This work provides new insight into fundamental mechanisms of macropinocytic uptake and processing and suggests new ways to interfere with or exploit macropinocytosis in mutant and other tumors.

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“…For example, pharmacological depolymerization of actin results in an increased number of actin waves in Dictyostelium (Bretschneider et al, 2009). A similar observation was made in fibroblasts, where actin waves take form of "circular dorsal ruffles," which are nonadhesive actin structures found on the dorsal side of some migrating cells (Bernitt, Döbereiner, Gov, & Yochelis, 2017;Bernitt, Koh, Gov, & Döbereiner, 2015;Chhabra & Higgs, 2007).…”

Section: Functions Of the Actin Wavefrontmentioning

confidence: 56%

A calcium‐mediated actin redistribution at egg activation in Drosophila

York-Andersen

Wood

et al. 2019

Molecular Reproduction Devel

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Egg activation is the essential process in which mature oocytes gain the competency to proceed into embryonic development. Many events of egg activation are conserved, including an initial rise of intracellular calcium. In some species, such as echinoderms and mammals, changes in the actin cytoskeleton occur around the time of fertilization and egg activation. However, the interplay between calcium and actin during egg activation remains unclear. Here, we use imaging, genetics, pharmacological treatment, and physical manipulation to elucidate the relationship between calcium and actin in living Drosophila eggs. We show that, before egg activation, actin is smoothly distributed between ridges in the cortex of the dehydrated mature oocytes. At the onset of egg activation, we observe actin spreading out as the egg swells though the intake of fluid. We show that a relaxed actin cytoskeleton is required for the intracellular rise of calcium to initiate and propagate. Once the swelling is complete and the calcium wave is traversing the egg, it leads to a reorganization of actin in a wavelike manner. After the calcium wave, the actin cytoskeleton has an even distribution of foci at the cortex. Together, our data show that calcium resets the actin cytoskeleton at egg activation, a model that we propose to be likely conserved in other species.

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Fronts and waves of actin polymerization in a bistability-based mechanism of circular dorsal ruffles

Cited by 44 publications

References 54 publications

How cortical waves drive fission of motile cells

How cortical waves drive fission of motile cells

Merlin/ERM proteins regulate growth factor-induced macropinocytosis and receptor recycling by organizing the plasma membrane:cytoskeleton interface

A calcium‐mediated actin redistribution at egg activation in Drosophila

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