title: A resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement.
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.
authors.affiliation: Anatomy III/Cell Biology, BioMedCenter, Ludwig-Maximilians-University, Grosshaderner Str. 9, Planegg-Martinsried, Germany.
authors.forename: Nagendran
authors.initials: N
authors.lastname: Ramalingam
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Franke
authors.affiliation: Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH, Jülich 52425 Germany.
authors.forename: Evelin
authors.initials: E
authors.lastname: Jaschinski
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Winterhoff
authors.affiliation: Institute of Biotechnology, University of Helsinki, PO Box 56, Helsinki 00014, Finland.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Brühmann
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Junemann
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Meier
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Köln 50931, Germany.
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
authors.affiliation: Division of Molecular Biology, Ruder Bošković Institute, Bijenička 54, Zagreb 10000, Croatia.
authors.forename: Igor
authors.initials: I
authors.lastname: Weber
authors.affiliation: Institute of Biotechnology, University of Helsinki, PO Box 56, Helsinki 00014, Finland.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH, Jülich 52425 Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Merkel
authors.affiliation: Anatomy III/Cell Biology, BioMedCenter, Ludwig-Maximilians-University, Grosshaderner Str. 9, Planegg-Martinsried, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schleicher
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Faix
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D004023:Dictyostelium / Q000502:physiology*; D005260:Female; D008124:Locomotion; D008840:Microfilament Proteins / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D011817:Rabbits; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: D000199:Actins; C101203:IQ motif containing GTPase activating protein 1; D008840:Microfilament Proteins; D010716:Phosphatidylinositols; D015800:Protozoan Proteins; C101109:ctxA protein, Dictyostelium discoideum; C101110:ctxB protein, Dictyostelium discoideum; D020703:ras GTPase-Activating Proteins; D000205:Actomyosin; D024462:Myosin Type II