“Cells on the move reach forward with lamellipodia and filopodia, cytoplasmic sheets and rods supported by branched networks or tight bundles of actin filaments. Cells without functional lamellipodia are still highly motile but lose their ability to stay on track, report researchers at the Stowers Institute for Medical Research in the April 9, 2012, online issue of the Journal of Cell Biology.

Their study provides new insight into cell motility, a complex and integrated process, which, when gone awry, can lead to various disease conditions such as cancer metastasis, birth defects, cardiovascular disease and compromised immune function.

Many cell types migrate through surrounding tissue: nerve cells reaching for their final destination; immune cells on the prowl for intruding pathogens; fibroblast called in to close wounds and stray cancer cells that have escaped the confines of the primary tumor. They all use actin filaments to push at the front by constantly remodeling their actin cytoskeleton.

"Our work demonstrates that an actin-polymerizing factor known as the Arp2/3 complex plays a critical role in the formation of the dendritic array of actin fibers that forms the structural backbone of lamellipodia and helps drive the leading edge of the cell forward," says Stowers Investigator Rong Li, Ph.D., who led the study.

When pure actin polymerizes, elongation is energetically favored over nucleation resulting in long thin filaments. The Arp2/3 complex, which localizes to lamellipodia, was thought to help build the web of actin filaments that shapes lamellipodia by initiating the branching process. "But it had been unclear whether Arp2/3 is actually required for lamellipodia formation and how it would affect cell motility," Li explains.

Unlike previous studies, which had mostly relied on RNA interference to reduce the concentration of functional Arp2/3 complex and had reached conflicting conclusions, Li and her team opted for the genetic disruption of the ARP2/3 complex to determine its function in fibroblast cell motility…”

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