A resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement

Nagendran Ramalingam, Christof Franke, Evelin Jaschinski, Moritz Winterhoff, Yao Lu, Stefan Brühmann, Alexander Junemann, Helena Meier, Angelika A. Noegel, Igor Weber, Hongxia Zhao, Rudolf Merkel, Michael Schleicher and Jan Faix ()
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Nagendran Ramalingam: Anatomy III/Cell Biology, BioMedCenter, Ludwig-Maximilians-University
Christof Franke: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany
Evelin Jaschinski: Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH
Moritz Winterhoff: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany
Yao Lu: Institute of Biotechnology, University of Helsinki, PO Box 56, Helsinki 00014, Finland
Stefan Brühmann: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany
Alexander Junemann: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany
Helena Meier: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany
Angelika A. Noegel: Center for Biochemistry, Medical Faculty, University of Cologne
Igor Weber: Ruder Bošković Institute, Bijenička 54, Zagreb 10000, Croatia
Hongxia Zhao: Institute of Biotechnology, University of Helsinki, PO Box 56, Helsinki 00014, Finland
Rudolf Merkel: Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH
Michael Schleicher: Anatomy III/Cell Biology, BioMedCenter, Ludwig-Maximilians-University
Jan Faix: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract Cell migration is driven by the establishment of disparity between the cortical properties of the softer front and the more rigid rear allowing front extension and actomyosin-based rear contraction. However, how the cortical actin meshwork in the rear is generated remains elusive. Here we identify the mDia1-like formin A (ForA) from Dictyostelium discoideum that generates a subset of filaments as the basis of a resilient cortical actin sheath in the rear. Mechanical resistance of this actin compartment is accomplished by actin crosslinkers and IQGAP-related proteins, and is mandatory to withstand the increased contractile forces in response to mechanical stress by impeding unproductive blebbing in the rear, allowing efficient cell migration in two-dimensional-confined environments. Consistently, ForA supresses the formation of lateral protrusions, rapidly relocalizes to new prospective ends in repolarizing cells and is required for cortical integrity. Finally, we show that ForA utilizes the phosphoinositide gradients in polarized cells for subcellular targeting.

Date: 2015
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DOI: 10.1038/ncomms9496

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