Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion

Kris A DeMali; Christy A Barlow; Keith Burridge

doi:10.1083/jcb.200206043

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Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion

Journal article

Open access

Peer reviewed

Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion

Kris A DeMali, Christy A Barlow and Keith Burridge

The Journal of cell biology, Vol.159(5), pp.881-891

12/09/2002

DOI: 10.1083/jcb.200206043

PMCID: PMC2173392

PMID: 12473693

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Abstract

Cell migration involves many steps, including membrane protrusion and the development of new adhesions. Here we have investigated whether there is a link between actin polymerization and integrin engagement. In response to signals that trigger membrane protrusion, the actin-related protein (Arp)2/3 complex transiently binds to vinculin, an integrin-associated protein. The interaction is regulated, requiring phosphatidylinositol-4,5-bisphosphate and Rac1 activation, and is sufficient to recruit the Arp2/3 complex to new sites of integrin aggregation. Binding of the Arp2/3 complex to vinculin is direct and does not depend on the ability of vinculin to associate with actin. We have mapped the binding site for the Arp2/3 complex to the hinge region of vinculin, and a point mutation in this region selectively blocks binding to the Arp2/3 complex. Compared with WT vinculin, expression of this mutant in vinculin-null cells results in diminished lamellipodial protrusion and spreading on fibronectin. The recruitment of the Arp2/3 complex to vinculin may be one mechanism through which actin polymerization and membrane protrusion are coupled to integrin-mediated adhesion.

Green Fluorescent Proteins

Embryo, Mammalian

Humans

Actins - metabolism

Vinculin - metabolism

Extracellular Matrix - metabolism

Phosphatidylinositol 3-Kinases - antagonists & inhibitors

Integrins - metabolism

Recombinant Fusion Proteins - metabolism

Phosphatidylinositol 3-Kinases - pharmacology

Cytoskeletal Proteins - metabolism

Cell Line

Cells, Cultured

Binding Sites - genetics

Cell Adhesion

Vinculin - chemistry

Point Mutation

Animals

Vinculin - genetics

Androstadienes - pharmacology

Pseudopodia - metabolism

Actin-Related Protein 2

Fibronectins - physiology

Protein Binding

Actin-Related Protein 3

Vinculin - antagonists & inhibitors

Mice

Epidermal Growth Factor - pharmacology

HeLa Cells

3T3 Cells

rac1 GTP-Binding Protein - metabolism

Cell Movement

Luminescent Proteins - metabolism

Details

Title: Subtitle: Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion
Creators: Kris A DeMali - Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. kdemali@med.unc.edu
Christy A Barlow
Keith Burridge
Resource Type: Journal article
Publication Details: The Journal of cell biology, Vol.159(5), pp.881-891
Publisher: United States
DOI: 10.1083/jcb.200206043
PMID: 12473693
PMCID: PMC2173392
ISSN: 0021-9525
eISSN: 1540-8140
Grant note: GM29860 / NIGMS NIH HHS HL45100 / NHLBI NIH HHS R01 GM029860 / NIGMS NIH HHS F32 GM020610 / NIGMS NIH HHS P01 HL045100 / NHLBI NIH HHS GM20610 / NIGMS NIH HHS
Language: English
Date published: 12/09/2002
Academic Unit: Dermatology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984024548502771

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