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 of actin, but they also bind to proteins called integrins.
Integrins are long molecules that pierce the membrane, leaving one end inside the cell and the other end firmly attached to the outside surface along which the cell is moving, according to Tina Izard, Ph.D., an associate member of Hematology-Oncology at St. Jude and the paper's senior author. Integrin's outside end is like a foot that is planted firmly on the ground but does not move, Izard said. Alpha-actinin molecules bound to the skeleton also bind to the end of integrin that is inside the cell. When the cell moves, stress on the "foot" part of the integrin outside the cell is transmitted into the cell to the other end of integrin. From there, the stress shifts to the alpha- actinin molecules that are also bound to the actin rods of the skeleton.