title: Kank2 activates talin, reduces force transduction across integrins and induces central adhesion formation.
abstract: Integrin-based adhesions play critical roles in cell migration. Talin activates integrins and flexibly connects integrins to the actomyosin cytoskeleton, thereby serving as a 'molecular clutch' that transmits forces to the extracellular matrix to drive cell migration. Here we identify the evolutionarily conserved Kank protein family as novel components of focal adhesions (FAs). Kank proteins accumulate at the lateral border of FAs, which we term the FA belt, and in central sliding adhesions, where they directly bind the talin rod domain through the Kank amino-terminal (KN) motif and induce talin and integrin activation. In addition, Kank proteins diminish the talin-actomyosin linkage, which curbs force transmission across integrins, leading to reduced integrin-ligand bond strength, slippage between integrin and ligand, central adhesion formation and sliding, and reduced cell migration speed. Our data identify Kank proteins as talin activators that decrease the grip between the integrin-talin complex and actomyosin to regulate cell migration velocity.
authors.affiliation: Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Tseng
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Tan
authors.affiliation: CytoMorpho Lab, Biosciences &Biotechnology Institute of Grenoble, UMR5168, CEA/INRA/CNRS/Université, 38054 Grenoble-Alpes, Grenoble, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Senger
authors.affiliation: CytoMorpho Lab, Biosciences &Biotechnology Institute of Grenoble, UMR5168, CEA/INRA/CNRS/Université, 38054 Grenoble-Alpes, Grenoble, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Kurzawa
authors.affiliation: Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Dedden
authors.affiliation: Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Naoko
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Anita A
authors.initials: AA
authors.lastname: Wasik
authors.affiliation: CytoMorpho Lab, Biosciences &Biotechnology Institute of Grenoble, UMR5168, CEA/INRA/CNRS/Université, 38054 Grenoble-Alpes, Grenoble, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Thery
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Dunn
authors.affiliation: Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D016608:Talin / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D016023:Integrins; C538755:Kank1 protein, mouse; D016608:Talin; D016596:Vinculin