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Molecular ballet unravels, links proteins so cell can direct own movement

As a cell moves forward, physical stress on its skeleton triggers molecular fingers and arms to grasp each other in reinforcing links that stabilize the skeleton, according to images produced by investigators at St. Jude Children's Research Hospital.

The images show how a protein called alpha-actinin partly unravels its structure to free an internal molecular "arm" that reaches out to another protein, called vinculin. This triggers vinculin to partly unravel as well, freeing several molecular "fingers" that assume a shape that allows alpha-actinin to bind to its partner.

The researchers used a technique called X-ray crystallography to create these images, which help explain how alpha-actinin recruits vinculin to help it brace the cell's skeleton during the physically stressful process of cell movement. A report on this work, scheduled for the July 15 issue of Molecular and Cellular Biology, appears in the prepublication online issue.

The discovery is important because without vinculin to reinforce its skeleton, the cell would move rapidly and randomly, making purposeful motion impossible, the researchers said. That means cells could not migrate properly in the developing embryo to take up their final positions, leaving the embryo to wither and die; yet the ability to move purposefully also helps individual cancer cells break away from a tumor and spread to other parts of the body, a process called metastasis. Therefore, discovering how cells direct their movements could help researchers better understand how embryos develop and how some cancers spread.

The cell's skeleton is a network of long rows of a protein called actin linked together by molecules of alpha-actinin. This configuration gives the skeleton a network structure in which many rows of actin are held together in a grid, somewhat like a checkerboard. Along the edge of the skeleton, near the cell membrane, the alpha-actinin molecules do double duty. They not only hold together rows
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Contact: Carrie Strehlau
Carrie.Strehlau@stjude.org
901-495-2295
St. Jude Children's Research Hospital
11-Jul-2005


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