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@ARTICLE{Litschko:860817,
author = {Litschko, Christof and Brühmann, Stefan and Csiszár,
Agnes and Stephan, Till and Dimchev, Vanessa and
Damiano-Guercio, Julia and Junemann, Alexander and Körber,
Sarah and Winterhoff, Moritz and Nordholz, Benjamin and
Ramalingam, Nagendran and Peckham, Michelle and Rottner,
Klemens and Merkel, Rudolf and Faix, Jan},
title = {{F}unctional integrity of the contractile actin cortex is
safeguarded by multiple {D}iaphanous-related formins},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {116},
number = {9},
issn = {1091-6490},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {FZJ-2019-01472},
pages = {3594-3603},
year = {2019},
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 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.},
cin = {ICS-7},
ddc = {500},
cid = {I:(DE-Juel1)ICS-7-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30808751},
UT = {WOS:000459694400044},
doi = {10.1073/pnas.1821638116},
url = {https://juser.fz-juelich.de/record/860817},
}