CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left-right symmetry breaking

Middelkoop, Teije C.; Garcia-Baucells, Júlia; Quintero-Cadena, Porfirio; Pimpale, Lokesh; Yazdi, Shahrzad; Sternberg, Paul W.; Groß, Peter; Grill, Stephan W.

doi:10.1101/2021.01.08.425924

Cited by 4 publications

(1 citation statement)

References 105 publications

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“…The development of left-right asymmetry, directed by the actin cytoskeleton, was observed in individual cells and cell collectives in vitro (Chen et al, 2012; Tee et al, 2015; Wan et al, 2011), as well as in a wide variety of in vivo developmental systems, such as Caenorhabditis. elegans oocytes (Middelkoop et al, 2021; Naganathan et al, 2014), Drosophila hindgut and genitalia (Hozumi et al, 2006; Lebreton et al, 2018; Spéder et al, 2006; Taniguchi et al, 2011), and in snails, presenting a classic example of biological chirality (Abe and Kuroda, 2019; Davison et al, 2016; Kuroda et al, 2016). Altogether these data suggest that specific actin filament structures, based on actin-associated proteins, such as diverse formins (DAAM1, Cyk1, snail Dia1) and myosins (1D and 1C), can translate and extend the asymmetric helical structure of actin filaments into asymmetric cellular and multicellular morphologies.…”

Section: Introductionmentioning

confidence: 99%

Chiral growth of adherent filopodia

Chung

Kozlov

et al. 2022

Preprint

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Adherent filopodia are elongated finger-like membrane protrusions, extending from the edges of diverse cell types and participating in cell adhesion, spreading, migration and environmental sensing. The formation and elongation of filopodia are driven by the polymerization of parallel actin filaments, comprising the filopodia cytoskeletal core. Here, we report that adherent filopodia, formed during the spreading of cultured cells on galectin-8-coated substrates, tend to change the direction of their extension in a chiral fashion, acquiring a left-bent shape. Cryo-electron tomography examination indicated that turning of the filopodia tip to the left is accompanied by the displacement of the actin core bundle to the right of the filopodia midline. Reduction of the adhesion to galectin-8 by treatment with thiodigalactoside abolished the filopodia chirality. By modulating the expression of a variety of actin-associated filopodia proteins, we identified myosin-X and formin DAAM1 as major filopodia chirality promoting factors. Formin mDia1, actin filament elongation factor VASP, and actin filament crosslinker fascin were also shown to be involved. Thus, the simple actin cytoskeleton of filopodia, together with a small number of associated proteins are sufficient to drive a complex navigation process, manifested by the development of left-right asymmetry in these cellular protrusions.

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Section: Introductionmentioning

confidence: 99%

Chiral growth of adherent filopodia

Chung

Kozlov

et al. 2022

Preprint

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CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left–right symmetry breaking

Middelkoop

Garcia-Baucells

Quintero-Cadena

et al. 2021

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

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Proper left–right symmetry breaking is essential for animal development, and in many cases, this process is actomyosin-dependent. In Caenorhabditis elegans embryos active torque generation in the actomyosin layer promotes left–right symmetry breaking by driving chiral counterrotating cortical flows. While both Formins and Myosins have been implicated in left–right symmetry breaking and both can rotate actin filaments in vitro, it remains unclear whether active torques in the actomyosin cortex are generated by Formins, Myosins, or both. We combined the strength of C. elegans genetics with quantitative imaging and thin film, chiral active fluid theory to show that, while Non-Muscle Myosin II activity drives cortical actomyosin flows, it is permissive for chiral counterrotation and dispensable for chiral symmetry breaking of cortical flows. Instead, we find that CYK-1/Formin activation in RhoA foci is instructive for chiral counterrotation and promotes in-plane, active torque generation in the actomyosin cortex. Notably, we observe that artificially generated large active RhoA patches undergo rotations with consistent handedness in a CYK-1/Formin–dependent manner. Altogether, we conclude that CYK-1/Formin–dependent active torque generation facilitates chiral symmetry breaking of actomyosin flows and drives organismal left–right symmetry breaking in the nematode worm.

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Septins and a formin have distinct functions in anaphase chiral cortical rotation in the C.eleganszygote

Zaatri

Perry

Maddox

2020

Preprint

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Many cells and tissues exhibit chirality that stems from the chirality of constituent proteins and polymers. For example, the C. elegans zygote undergoes an actomyosin-driven chiral rotation in which the entire cortex is displaced circumferentially around the division plane during anaphase. This phenomenon thus relates to how force and chirality are translated across scales. Although it is known that actomyosin contractility drives this rotation, its molecular mechanisms are incompletely understood. Septins are candidates for contributing to cell-scale chirality due to their ability to anchor and organize the actomyosin cytoskeleton. Here, we report that septins are required for anaphase cortical rotation. In contrast, the formin CYK-1, which we found to be enriched in the posterior in early anaphase, is not required for cortical rotation, but contributes to its chirality. Simultaneous loss of septin and CYK-1 function led to highly abnormal and often reversed cortical rotation. We propose a model by which anaphase cortical contractility is biased in a chiral fashion via interaction between the circumferential cytokinetic ring and perpendicular, longitudinal formin-based actin bundles that have accumulated torsional stress during formin-based polymerization. Our findings thus shed light on the molecular and physical bases for cellular chirality in the C. elegans zygote. We also identify conditions in which chiral rotation fails but animals are developmentally viable, opening avenues for future work on the relationship between early embryonic cellular chirality and animal body plan.

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CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left-right symmetry breaking

Cited by 4 publications

References 105 publications

Chiral growth of adherent filopodia

Chiral growth of adherent filopodia

CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left–right symmetry breaking

Septins and a formin have distinct functions in anaphase chiral cortical rotation in the C.eleganszygote

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