title: VASP-dependent regulation of actin cytoskeleton rigidity, cell adhesion, and detachment.
abstract: Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) proteins are established regulators of actin-based motility, platelet aggregation, and growth cone guidance. However, the molecular mechanisms involved essentially remain elusive. Here we report on a novel mechanism of VASP action, namely the regulation of tensile strength, contractility, and rigidity of the actin cytoskeleton. Compared to wild-type cells fibroblasts derived from VASP-deficient mice have thicker and more stable actin stress fibres. Furthermore focal adhesions are enlarged, myosin light chain phosphorylation is increased, and the rigidity of the filament-supported plasma membrane is elevated about three- to fourfold, as is evident from atomic force microscopy. Moreover, fibronectin-coated beads adhere stronger to the surface of VASP-deficient cells. The resistance of these beads to mechanical displacement by laser tweezers is dramatically increased in an F-actin-dependent mode. Cytoskeletal stabilization coincides with slower cell adhesion and detachment, while overall adhesion is increased. Interestingly, many of these effects observed in VASP (-/-) cells are recapitulated in VASP-overexpressing cells, hinting towards a balanced stoichiometry necessary for appropriate VASP function. Taken together, our results suggest that VASP regulates surface protrusion formation and cell adhesion through modulation of the mechanical properties of the actin cytoskeleton.
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany.
authors.forename: Annette B
authors.initials: AB
authors.lastname: Galler
authors.forename: Maísa I
authors.initials: MI
authors.lastname: García Arguinzonis
authors.forename: Werner
authors.initials: W
authors.lastname: Baumgartner
authors.forename: Monika
authors.initials: M
authors.lastname: Kuhn
authors.forename: Albert
authors.initials: A
authors.lastname: Smolenski
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
authors.forename: Matthias
authors.initials: M
authors.lastname: Reinhard
mesh_terms: D000199:Actins / Q000648:ultrastructure*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000502:physiology*; D003599:Cytoskeleton / Q000648:ultrastructure*; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000172:deficiency / Q000502:physiology*; D018625:Microscopy, Atomic Force; D008863:Microspheres; D008954:Models, Biological; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins / Q000172:deficiency / Q000502:physiology*; D010766:Phosphorylation; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D008840:Microfilament Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein