Novel cytokinetic ring components drive negative feedback in cortical contractility - Sorbonne Université
Journal Articles Molecular Biology of the Cell Year : 2020

Novel cytokinetic ring components drive negative feedback in cortical contractility

Abstract

Actomyosin cortical contractility drives many cell shape changes including cytokinetic furrowing. While positive regulation of contractility is well characterized, counterbalancing negative regulation and mechanical brakes are less well understood. The small GTPase RhoA is a central regulator, activating cortical actomyosin contractility during cytokinesis and other events. Here we report how two novel cytokinetic ring components, GCK-1 (germinal center kinase-1) and CCM-3 (cerebral cavernous malformations-3), participate in a negative feedback loop among RhoA and its cytoskeletal effectors to inhibit contractility. GCK-1 and CCM-3 are recruited by active RhoA and anillin to the cytokinetic ring, where they in turn limit RhoA activity and contractility. This is evidenced by increased RhoA activity, anillin and nonmuscle myosin II in the cytokinetic ring, and faster cytokinetic furrowing, following depletion of GCK-1 or CCM-3. GCK-1 or CCM-3 depletion also reduced RGA-3 levels in pulses and increased baseline RhoA activity and pulsed contractility during zygote polarization. Together, our results suggest that GCK-1 and CCM-3 regulate cortical actomyosin contractility via negative feedback. These findings have implications for the molecular and cellular mechanisms of cerebral cavernous malformation pathologies.

Domains

Genetics
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Origin Publication funded by an institution

Dates and versions

hal-03244176 , version 1 (01-06-2021)

Identifiers

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Kathryn Rehain Bell, Michael Werner, Anusha Doshi, Daniel Cortes, Adam Sattler, et al.. Novel cytokinetic ring components drive negative feedback in cortical contractility. Molecular Biology of the Cell, 2020, 31 (15), pp.1623-1636. ⟨10.1091/mbc.E20-05-0304)⟩. ⟨hal-03244176⟩
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