Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex

Bryan Serrels; Alan Serrels; Valerie G Brunton; Mark Holt; Gordon W McLean; Christopher H Gray; Gareth E Jones; Margaret C Frame

doi:10.1038/ncb1626

Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex

Bryan Serrels, Alan Serrels, Valerie G Brunton, Mark Holt, Gordon W McLean, Christopher H Gray, Gareth E Jones, Margaret C Frame

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

Abstract / Description of output

Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery.

Original language	English
Pages (from-to)	1046-56
Number of pages	11
Journal	Nature Cell Biology
Volume	9
Issue number	9
DOIs	https://doi.org/10.1038/ncb1626
Publication status	Published - Sept 2007

Keywords / Materials (for Non-textual outputs)

Actin-Related Protein 2-3 Complex
Actins
Amino Acid Sequence
Animals
Cell Adhesion
Cells, Cultured
Focal Adhesion Protein-Tyrosine Kinases
Integrins
Mice
Mice, Knockout
Molecular Sequence Data
Phosphorylation
Protein Binding
Protein Structure, Tertiary
Pseudopodia
Stress Fibers
Tyrosine
Wiskott-Aldrich Syndrome Protein, Neuronal

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@article{b6b587016eab4bd5ab9552174986b714,

title = "Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex",

abstract = "Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery.",

keywords = "Actin-Related Protein 2-3 Complex, Actins, Amino Acid Sequence, Animals, Cell Adhesion, Cells, Cultured, Focal Adhesion Protein-Tyrosine Kinases, Integrins, Mice, Mice, Knockout, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Pseudopodia, Stress Fibers, Tyrosine, Wiskott-Aldrich Syndrome Protein, Neuronal",

author = "Bryan Serrels and Alan Serrels and Brunton, {Valerie G} and Mark Holt and McLean, {Gordon W} and Gray, {Christopher H} and Jones, {Gareth E} and Frame, {Margaret C}",

year = "2007",

month = sep,

doi = "10.1038/ncb1626",

language = "English",

volume = "9",

pages = "1046--56",

journal = "Nature Cell Biology",

issn = "1465-7392",

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T1 - Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex

AU - Serrels, Bryan

AU - Serrels, Alan

AU - Brunton, Valerie G

AU - Holt, Mark

AU - McLean, Gordon W

AU - Gray, Christopher H

AU - Jones, Gareth E

AU - Frame, Margaret C

PY - 2007/9

Y1 - 2007/9

N2 - Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery.

AB - Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery.

KW - Actin-Related Protein 2-3 Complex

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KW - Amino Acid Sequence

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KW - Cells, Cultured

KW - Focal Adhesion Protein-Tyrosine Kinases

KW - Integrins

KW - Mice

KW - Mice, Knockout

KW - Molecular Sequence Data

KW - Phosphorylation

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Pseudopodia

KW - Stress Fibers

KW - Tyrosine

KW - Wiskott-Aldrich Syndrome Protein, Neuronal

U2 - 10.1038/ncb1626

DO - 10.1038/ncb1626

M3 - Article

C2 - 17721515

SN - 1465-7392

VL - 9

SP - 1046

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JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 9

ER -

Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex

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Keywords / Materials (for Non-textual outputs)

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