Published online 2 May 2005. doi:10.1083/jcb1693iti1
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 3, 374-374
Integrins control migration style
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Migration is less persistent with ß1 integrin (top) than with ß3 integrin (bottom).
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Danen et al. (page 515) show that ß1 and ß3 integrins direct different types of motility, despite binding fibronectin with similar efficiencies. Cells expressing ß1 integrin move in a random manner, whereas cells with ß3 integrin expression move in a persistent fashion. The proteins control cell migration by altering the activities of the Rho GTPases RhoA and Rac, which in turn control three aspects of motility: lamellipodia formation; cytoskeletal polarization; and the dynamics of cell matrix adhesions.
The types of integrins expressed and their relative abundance change during dynamic processes such as wound healing and development. To understand the function of these shifts, Danen et al. studied GE11 cells that lack ß1 and express trace amounts of ß3. Previous work demonstrated these cells don't migrate well in a wound-healing assay.
When GE11 cells were transduced with ß3 (GEß3), they formed lamellipodia, had active cofilin, and migrated persistently. Cells transduced with ß1 integrin (GEß1) migrated in a wound healing assay but contained many actin stress fibers, phosphorylated inactive cofilin, and multiple random protrusions rather than a well-organized lamellipod. Inhibition of RhoA—which in its active form promotes stress fiber formation—activated cofilin in GEß1 cells, restoring persistent migration. By contrast, overexpression of Rac, which supports lamellipodia formation, was not sufficient to promote persistent migration in GEß1 cells. Thus the problem in GEß1 cells seems to be too many stress fibers rather than too little lamellipodia formation.
Just how the different ß integrins connect to distinct Rho GTPases to control migration is not clear. Switching the intracellular tails between integrins doesn't change their effect on Rho GTPases (Danen et al. 2002. J. Cell Biol. 159:1071–1086), so the researchers think that the signaling differences result from different integrins working with different coreceptors. Syndecans may fit that role—they interact functionally with integrins and they regulate Rho GTPases. 
Rabiya S. Tuma
rabiya{at}nasw.org
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