Grant: Project Grant

The major architectural protein in cells is actin, and actin filaments play crucial roles in all cells. Filamin was one of the first actin-binding proteins characterized. It is a rod-like protein with a dimerization (self-association) domain at one end and an actin-binding domain at the other end. Filamin cross-links actin filaments into a loose meshwork in non-muscle cells. In muscle cells filamin function is not well understood, except that it localizes to Z-lines and causes severe muscle disorders when mutated. Here we propose to analyze the molecular and cell biological function of filamin in muscle cells using the fruit fly Drosophila as a model system. Our recent data indicate that filamin mutations have severe, but distinct muscle defects, depending on whether the actin-binding domain or the self-association domain of filamin is mutated. Our proposed biochemical and genetic experiments will provide insight into filamin binding partners and how they function together to enable muscle contractility. This in turn will also provide information on how filamin mutations cause muscle disorders in humans.