Tropomodulin is a pointed-end actin filament capping protein that also binds to tropomyosin. In muscle cells, tropomodulin is responsible for regulating the length of actin filaments in the sarcomere. While the function of tropomodulin in muscle is well characterized, a novel isoform of tropomodulin was recently found in nonmuscle cells, where it has been implicated as a negative regulator of actin filament dynamics at the leading edge of crawling cells. It is our hypothesis that tropomodulin is also likely to be involved in the regulation of other cellular actin structures. Specifically, I plan to investigate the role of tropomodulin in regulating stress fibers in endothelial cells. Further, I will characterize the interaction of tropomodulin with long versus short tropomyosin isoforms and test whether this interaction is required for the function of tropomodulin in stress fibers. In addition, evidence suggests that some tropomodulin isoforms may be phosphorylated. I will confirm that tropomodulin phosphorylation occurs in endothelial cells and investigate whether phosphorylation is responsible for regulating tropomodulin activity. In this way, we hope to further the understanding of cellular actin architecture and the role tropomodulin has in regulating it.
| Weber, Kari L; Fischer, Robert S; Fowler, Velia M (2007) Tmod3 regulates polarized epithelial cell morphology. J Cell Sci 120:3625-32 |
