Revealing another part of the story of muscle development, Johns Hopkins researchers have shown how the cytoskeleton from one muscle cell builds finger-like projections that invade into another muscle cell's territory, eventually forcing the cells to combine.
Such muscle cell fusion, the researchers say, is not only important for understanding normal muscle growth, but also muscle regeneration after injury or disease. The work, they believe, could further development of therapies for muscular dystrophy or age-related muscle wasting.
Their report on muscle cell cytoskeletons, published in Developmental Cell May 17, adds detail to a previous study last year showing that actin a main building block of the cell's cytoskeleton is required to form those finger-like projections and stimulate muscle cell merges. The new discovery outlines the intricate dance required among cytoskeleton-regulating proteins to precisely construct protrusions that promote muscle cell merging. Specifically, the Johns Hopkins team uncovered the activity of a regulatory protein known as "Blown Fuse," aptly named because muscle cells lacking this protein fail to fuse.
"Blown Fuse was found to play a role in muscle cell fusion 14 years ago," says Elizabeth Chen, Ph.D. assistant professor of molecular biology and genetics, "and now we know how Blown Fuse regulates the dynamics of the cytoskeleton to facilitate the invasion of one muscle cell by another."
In a test tube, the researchers showed that the protein, Blown Fuse, disrupts the complex formed by the protein duo WASP and WIP, which are known regulators of the actin cytoskeleton. "Blown Fuse does so by a competitive binding mechanism it binds to the same site in WIP as WASP does," says Rui Duan, a postdoctoral fellow in Chen's lab and a co-first author of the study.
The researchers knew that the WASP-WIP protein duo binds to the growing ends of actin filaments, protecting these ends
|Contact: Vanessa McMains|
Johns Hopkins Medical Institutions