Functional integrity of the contractile actin cortex is safeguarded by multiple Diaphanous-related formins

Proceedings of the National Academy of Sciences of the United States of America
Christof LitschkoJan Faix

Abstract

The contractile actin cortex is a thin layer of filamentous actin, myosin motors, and regulatory proteins beneath the plasma membrane crucial to cytokinesis, morphogenesis, and cell migration. However, the factors regulating actin assembly in this compartment are not well understood. Using the Dictyostelium model system, we show that the three Diaphanous-related formins (DRFs) ForA, ForE, and ForH are regulated by the RhoA-like GTPase RacE and synergize in the assembly of filaments in the actin cortex. Single or double formin-null mutants displayed only moderate defects in cortex function whereas the concurrent elimination of all three formins or of RacE caused massive defects in cortical rigidity and architecture as assessed by aspiration assays and electron microscopy. Consistently, the triple formin and RacE mutants encompassed large peripheral patches devoid of cortical F-actin and exhibited severe defects in cytokinesis and multicellular development. Unexpectedly, many forA - /E-/H- and racE - mutants protruded efficiently, formed multiple exaggerated fronts, and migrated with morphologies reminiscent of rapidly moving fish keratocytes. In 2D-confinement, however, these mutants failed to properly polarize and recruit myo...Continue Reading

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Citations

Sep 26, 2019·Essays in Biochemistry·Matthias SchaksKlemens Rottner
Jan 16, 2020·Molecular Biology of the Cell·Mary EckeGünther Gerisch
Dec 12, 2019·F1000Research·Simona BuraccoRobert Insall
Sep 29, 2020·Platelets·Malou ZuidscherwoudeSteven G Thomas
Feb 12, 2021·PloS One·Peter J M van Haastert
Sep 18, 2020·Journal of the Mechanical Behavior of Biomedical Materials·Xiaobo WangDavid Kennedy
Aug 13, 2021·PLoS Computational Biology·Daisuke ImotoSatoshi Sawai

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