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

Christof Litschko(Medizinische Hochschule Hannover), Stefan Brühmann(Medizinische Hochschule Hannover), Ágnes Csiszár(Forschungszentrum Jülich), Till Stephan(Medizinische Hochschule Hannover), Vanessa Dimchev(Helmholtz Centre for Infection Research), Julia Damiano-Guercio(Medizinische Hochschule Hannover), Alexander Junemann(Medizinische Hochschule Hannover), Sarah Körber(Medizinische Hochschule Hannover), Moritz Winterhoff(Medizinische Hochschule Hannover), Benjamin Nordholz(Medizinische Hochschule Hannover), Nagendran Ramalingam(Brigham and Women's Hospital), Michelle Peckham(University of Leeds), Klemens Rottner(Helmholtz Centre for Infection Research), Rudolf Merkel(Forschungszentrum Jülich), Jan Faix(Medizinische Hochschule Hannover)
Proceedings of the National Academy of Sciences
February 11, 2019
10.1073/pnas.1821638116
Cited by 42Open Access
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Abstract

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 myosin II to the cell rear essential for migration. Cells arrested in these conditions displayed dramatically amplified flow of cortical actin filaments, as revealed by total internal reflection fluorescence (TIRF) imaging and iterative particle image velocimetry (PIV). Consistently, individual and combined, CRISPR/Cas9-mediated disruption of genes encoding mDia1 and -3 formins in B16-F1 mouse melanoma cells revealed enhanced frequency of cells displaying multiple fronts, again accompanied by defects in cell polarization and migration. These results suggest evolutionarily conserved functions for formin-mediated actin assembly in actin cortex mechanics.

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