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Dev Cell. 2013 Dec 9;27(5):545-59. doi: 10.1016/j.devcel.2013.11.003.

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

Author information

1
Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: ti2170@columbia.edu.
2
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
3
Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA.
4
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
5
Randall Division of Cell and Molecular Biophysics and Cardiovascular Division, King's College London, London SE1 1UL, UK.
6
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.

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.

PMID:
24331927
PMCID:
PMC3890431
DOI:
10.1016/j.devcel.2013.11.003
[Indexed for MEDLINE]
Free PMC Article

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