Researchers define role of vinculin protein in enabling cell mobility

Published on August 16, 2013 at 3:54 AM · No Comments

Researchers at the University of North Carolina and the National Institutes for Health have defined the role of the protein vinculin in enabling cell movement.

In a paper published in the Journal of Cell Biology, Sharon Campbell, PhD, professor of Biochemistry and Biophysics and member of UNC Lineberger Comprehensive Cancer Center, and Clare Waterman of the National Heart, Lung and Blood Institute at the National Institutes of Health showed that cell mobility occurs through the interactions between the protein vinculin and the cytoskeletal lattice formed by the protein actin. By physically binding to the actin that makes up the cytoskeleton, vinculin operates as a form of molecular clutch transferring force and controlling cell motion.

"The hypothesis with the molecular clutch is that you get this kind of treadmilling effect. If you have an analogy with a car, the car is running in neutral. You get something pushing forward and something pulling behind, and you really don't have much effect on the cell. You have a lot of energy that's lost. But if it engages, this slows the retrogade flow and the actin polymerization pushes the leading edge forward so that it can move," said Campbell.

In this context, vinculin localizes to cellular components called focal adhesions, with over a hundred different proteins, and has been postulated to play a critical role as a molecular clutch. These adhesions can be thought of as wheels, taking the energy from the actin cytoskeleton and using it to move the whole cell across a substrate. So how important is this one protein, vinculin, in regulating cell movement?

Studies with knockout models that deactivated vinculin show that the cell still can move without the protein, but the movement becomes more chaotic. This can impact cell processes such as organ development. Embryonic mice without vinculin, for example, do not develop in the womb.

"Vinculin makes cells almost smarter, in a way. It really helps the cells decide if they are going to stay put or if they are going to go. And if they are going to go, it is going to be in a direction where there is a reason to go to. If you knock vinculin out, they lose that. They lose the anchoring effect. They move more easily, but they also move more randomly," said Peter Thompson, paper co-author and graduate student in the Campbell lab.

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