title: FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration.
abstract: Matrix adhesions provide critical signals for cell growth or differentiation. They form through a number of distinct steps that follow integrin binding to matrix ligands. In an early step, integrins form clusters that support actin polymerization by an unknown mechanism. This raises the question of how actin polymerization occurs at the integrin clusters. We report here that a major formin in mouse fibroblasts, FHOD1, is recruited to integrin clusters, resulting in actin assembly. Using cell-spreading assays on lipid bilayers, solid substrates, and high-resolution force-sensing pillar arrays, we find that knockdown of FHOD1 impairs spreading, coordinated application of adhesive force, and adhesion maturation. Finally, we show that targeting of FHOD1 to the integrin sites depends on the direct interaction with Src family kinases and is upstream of the activation by Rho kinase. Thus, our findings provide insights into the mechanisms of cell migration with implications for development and disease.
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: ti2170@columbia.edu.
authors: Thomas
authors: T
authors: Iskratsch
authors: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors: Cheng-Han
authors: CH
authors: Yu
authors: Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA.
authors: Anurag
authors: A
authors: Mathur
authors: Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA.
authors: Shuaimin
authors: S
authors: Liu
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors: Virginie
authors: V
authors: Stévenin
authors: Randall Division of Cell and Molecular Biophysics and Cardiovascular Division, King's College London, London SE1 1UL, UK.
authors: Joseph
authors: J
authors: Dwyer
authors: Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA.
authors: James
authors: J
authors: Hone
authors: Randall Division of Cell and Molecular Biophysics and Cardiovascular Division, King's College London, London SE1 1UL, UK.
authors: Elisabeth
authors: E
authors: Ehler
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore. Electronic address: ms2001@columbia.edu.
authors: Michael
authors: M
authors: Sheetz
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D005326:Fetal Proteins / Q000235:genetics* / Q000378:metabolism*; D005333:Fetus / Q000166:cytology / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D022001:Focal Adhesions / Q000378:metabolism; D000080865:Formins; D055785:Gene Knockdown Techniques; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C586375:FHOD1 protein, mouse; D005326:Fetal Proteins; D000080865:Formins; D016023:Integrins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D019061:src-Family Kinases