Cell migration is driven by actin filament polymerization that pushes the leading edge of the cell forward, as well as F-actin retrograde flow. Focal adhesions (FAs) adhere the crawling cell to the underlying extracellular matrix (ECM), and are assembled and disassembled near the leading edge of the cell. Proteins of these FAs are believed to make up a “molecular clutch” that engages the retrograde F-actin flow, and a recent paper identifies the protein vinculin, an actin-binding protein, as a molecular clutch. Thievessen and colleagues investigated the effects of vinculin gene disruption in migrating fibroblasts, and found that vinculin is important in regulating F-actin organization and FA dynamics. Specifically, vinculin generates the ECM traction forces necessary for migration, and promotes FA formation and turnover. In the images above, a normal fibroblast (top) and a fibroblast lacking vinculin (bottom) show F-actin (green) and the lamellipodial protein cortactin (purple). Normal crawling fibroblasts have a sharply defined band of cortactin colocalized with F-actin at the leading edge, while vinculin mutants have a wider, less defined region of cortactin at the leading edge, suggesting the importance of vinculin in leading edge organization.
BONUS! Check out some cool movies from this paper here.
Thievessen I, Thompson PM, Berlemont S, Plevock KM, Plotnikov SV, Zemljic-Harpf A, Ross RS, Davidson MW, Danuser G, Campbell SL, & Waterman CM (2013). Vinculin-actin interaction couples actin retrograde flow to focal adhesions, but is dispensable for focal adhesion growth. originally published in the Journal of Cell Biology, 202 (1), 163-77 PMID: 23836933
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