title: Vinculin-dependent actin bundling regulates cell migration and traction forces.
abstract: Vinculin binding to actin filaments is thought to be critical for force transduction within a cell, but direct experimental evidence to support this conclusion has been limited. In the present study, we found mutation (R1049E) of the vinculin tail impairs its ability to bind F-actin, stimulate actin polymerization, and bundle F-actin in vitro. Further, mutant (R1049E) vinculin expressing cells are altered in cell migration, which is accompanied by changes in cell adhesion, cell spreading and cell generation of traction forces, providing direct evidence for the critical role of vinculin in mechanotransduction at adhesion sites. Lastly, we discuss the viability of models detailing the F-actin-binding surface on vinculin in the context of our mutational analysis.
authors.affiliation: *Department of Biochemistry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, U.S.A.
authors.forename: Karry M
authors.initials: KM
authors.lastname: Jannie
authors.affiliation: *Department of Biochemistry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, U.S.A.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Ellerbroek
authors.affiliation: †Woodruff School of Mechanical Engineering, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, U.S.A.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Zhou
authors.affiliation: *Department of Biochemistry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, U.S.A.
authors.forename: Sophia
authors.initials: S
authors.lastname: Chen
authors.affiliation: *Department of Biochemistry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, U.S.A.
authors.forename: David J
authors.initials: DJ
authors.lastname: Crompton
authors.affiliation: †Woodruff School of Mechanical Engineering, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, U.S.A.
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
authors.affiliation: *Department of Biochemistry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, U.S.A.
authors.forename: Kris A
authors.initials: KA
authors.lastname: DeMali
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D016596:Vinculin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000199:Actins; D016596:Vinculin