title: Fascin plays a role in stress fiber organization and focal adhesion disassembly.
abstract: Migrating cells nucleate focal adhesions (FAs) at the cell front and disassemble them at the rear to allow cell translocation. FAs are made of a multiprotein complex, the adhesome, which connects integrins to stress fibers made of mixed-polarity actin filaments [1-5]. Myosin II-driven contraction of stress fibers generates tensile forces that promote adhesion growth [6-9]. However, tension must be tightly controlled, because if released, FAs disassemble [3, 10-12]. Conversely, excess tension can cause abrupt cell detachment resulting in the loss of a major part of the adhesion [9, 12]. Thus, both adhesion growth and disassembly depend on tensile forces generated by stress fiber contraction, but how this contractility is regulated remains unclear. Here, we show that the actin-bundling protein fascin crosslinks the actin filaments into parallel bundles at the stress fibers' termini. Fascin prevents myosin II entry at this region and inhibits its activity in vitro. In fascin-depleted cells, polymerization of actin filaments at the stress fiber termini is slower, the actin cytoskeleton is reorganized into thicker stress fibers with a higher number of myosin II molecules, FAs are larger and less dynamic, and consequently, traction forces that cells exert on their substrate are larger. We also show that fascin dissociation from stress fibers is required to allow their severing by cofilin, leading to efficient disassembly of FAs.
authors.affiliation: Research Center, Institut Curie, 25 Rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 Rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Elkhatib
authors.affiliation: Research Center, Institut Curie, 25 Rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 Rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Neu
authors.affiliation: Lehrstuhl für Biophysik E27, Technische Universität München, 85748 Garching, Germany.
authors.forename: Carla
authors.initials: C
authors.lastname: Zensen
authors.affiliation: Lehrstuhl für Biophysik E27, Technische Universität München, 85748 Garching, Germany.
authors.forename: Kurt M
authors.initials: KM
authors.lastname: Schmoller
authors.affiliation: Research Center, Institut Curie, 25 Rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 Rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Louvard
authors.affiliation: Lehrstuhl für Biophysik E27, Technische Universität München, 85748 Garching, Germany.
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Bausch
authors.affiliation: Research Center, Institut Curie, 25 Rue d'Ulm, 75248 Paris Cedex 05, France; UMR168/CNRS, 25 Rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Timo
authors.initials: T
authors.lastname: Betz
authors.affiliation: Research Center, Institut Curie, 25 Rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 Rue d'Ulm, 75248 Paris Cedex 05, France. Electronic address: danijela.vignjevic@curie.fr.
authors.forename: Danijela Matic
authors.initials: DM
authors.lastname: Vignjevic
mesh_terms: D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D001696:Biomechanical Phenomena; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D022001:Focal Adhesions / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D024462:Myosin Type II / Q000378:metabolism; D058105:Polymerization; D022502:Stress Fibers / Q000378:metabolism*; D059008:Time-Lapse Imaging; D000097573:Red Fluorescent Protein
chemical_list: D000199:Actins; D002352:Carrier Proteins; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D024462:Myosin Type II; D000097573:Red Fluorescent Protein; C020324:fascin