FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration

Thomas Iskratsch; Cheng-Han Yu; Anurag Mathur; Shuaimin Liu; Virginie Stévenin; Joseph Dwyer; James Hone; Elisabeth Ehler; Michael Sheetz

doi:10.1016/j.devcel.2013.11.003

FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration

Thomas Iskratsch, Cheng-Han Yu, Anurag Mathur, Shuaimin Liu, Virginie Stévenin, Joseph Dwyer, James Hone, Elisabeth Ehler, Michael Sheetz

Research output: Contribution to journal › Article › peer-review

86 Citations (Scopus)

246 Downloads (Pure)

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.

Original language	English
Pages (from-to)	545-559
Number of pages	15
Journal	Developmental Cell
Volume	27
Issue number	5
DOIs	https://doi.org/10.1016/j.devcel.2013.11.003
Publication status	Published - 9 Dec 2013

Keywords

Actin Cytoskeleton
Amino Acid Sequence
Animals
Cell Adhesion
Cell Movement
Female
Fetal Proteins
Fetus
Fibroblasts
Focal Adhesions
Gene Knockdown Techniques
Integrins
Mice
Molecular Sequence Data
Nuclear Proteins
Pregnancy
RNA, Small Interfering
src-Family Kinases

Access to Document

10.1016/j.devcel.2013.11.003Licence: CC BY

DevCell_FHOD1 Is Needed for Directed Forces and Adhesion Maturation during Cell Spreading and MigrationFinal published version, 4.73 MBLicence: CC BY

Cite this

@article{95fb35a3819b4f76bfb35bce0fa777aa,

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.",

keywords = "Actin Cytoskeleton, Amino Acid Sequence, Animals, Cell Adhesion, Cell Movement, Female, Fetal Proteins, Fetus, Fibroblasts, Focal Adhesions, Gene Knockdown Techniques, Integrins, Mice, Molecular Sequence Data, Nuclear Proteins, Pregnancy, RNA, Small Interfering, src-Family Kinases",

author = "Thomas Iskratsch and Cheng-Han Yu and Anurag Mathur and Shuaimin Liu and Virginie St{\'e}venin and Joseph Dwyer and James Hone and Elisabeth Ehler and Michael Sheetz",

year = "2013",

month = dec,

day = "9",

doi = "10.1016/j.devcel.2013.11.003",

language = "English",

volume = "27",

pages = "545--559",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration

AU - Iskratsch, Thomas

AU - Yu, Cheng-Han

AU - Mathur, Anurag

AU - Liu, Shuaimin

AU - Stévenin, Virginie

AU - Dwyer, Joseph

AU - Hone, James

AU - Ehler, Elisabeth

AU - Sheetz, Michael

PY - 2013/12/9

Y1 - 2013/12/9

N2 - 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.

AB - 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.

KW - Actin Cytoskeleton

KW - Amino Acid Sequence

KW - Animals

KW - Cell Adhesion

KW - Cell Movement

KW - Female

KW - Fetal Proteins

KW - Fetus

KW - Fibroblasts

KW - Focal Adhesions

KW - Gene Knockdown Techniques

KW - Integrins

KW - Mice

KW - Molecular Sequence Data

KW - Nuclear Proteins

KW - Pregnancy

KW - RNA, Small Interfering

KW - src-Family Kinases

U2 - 10.1016/j.devcel.2013.11.003

DO - 10.1016/j.devcel.2013.11.003

M3 - Article

C2 - 24331927

SN - 1534-5807

VL - 27

SP - 545

EP - 559

JO - Developmental Cell

JF - Developmental Cell

IS - 5

ER -

FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration

Abstract

Keywords

Access to Document

Fingerprint

Cite this