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PMID: 12473693 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

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

The Journal of cell biology ·Vol. 159 ·No. 5 ·2002-12-09 ·Pages 881-91

DeMali KA, Barlow CA, Burridge K

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.

MeSH Terms
3T3 Cells Actin-Related Protein 2 Actin-Related Protein 3 Actins/metabolism Androstadienes/pharmacology Animals Binding Sites/genetics Cell Adhesion Cell Line Cell Movement Cells, Cultured Cytoskeletal Proteins/metabolism Embryo, Mammalian Epidermal Growth Factor/pharmacology Extracellular Matrix/metabolism Fibronectins/physiology Green Fluorescent Proteins HeLa Cells Humans Integrins/metabolism Luminescent Proteins/metabolism Mice Phosphatidylinositol 3-Kinases/pharmacology Phosphoinositide-3 Kinase Inhibitors Point Mutation Protein Binding Pseudopodia/metabolism Recombinant Fusion Proteins/metabolism Vinculin/antagonists & inhibitors,chemistry,genetics,metabolism Wortmannin rac1 GTP-Binding Protein/metabolism
Chemicals
ACTR2 protein, human ACTR3 protein, human Actin-Related Protein 2 Actin-Related Protein 3 Actins Actr2 protein, mouse Actr3 protein, mouse Androstadienes Cytoskeletal Proteins Fibronectins Integrins Luminescent Proteins Phosphoinositide-3 Kinase Inhibitors Recombinant Fusion Proteins Vinculin Green Fluorescent Proteins Epidermal Growth Factor rac1 GTP-Binding Protein Wortmannin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
DeMali Kris A
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. kdemali@med.unc.edu
Barlow Christy A
Burridge Keith
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200206043
Email
kdemali@med.unc.edu
Published
2002-12-09
Epub
2002-00-09
Pages
881-91
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173392
Subset
IM
Grants
NIGMS NIH HHS · GM29860 · United States
NIGMS NIH HHS · GM20610 · United States
NIGMS NIH HHS · F32 GM020610 · United States
NIGMS NIH HHS · R01 GM029860 · United States
NHLBI NIH HHS · HL45100 · United States
NHLBI NIH HHS · P01 HL045100 · United States
External Links
PubMed source DOI: 10.1083/jcb.200206043 PMC Full Text View journal details
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