Grant: Operating Grant

We have identified the LIM domain protein Zasp, which is involved in connecting cells to their environment. This connection is mediated by integrins, proteins that sit in the plasma membrane surrounding each cell. Zasp carries a protein domain that targets it to the intracellular side of integrin adhesion sites, where Zasp is crucial for the assembly and regulation of integrin adhesion sites. Zasp functions largely in muscles, and in muscles integrin adhesion sites connect muscles to tendons and along the length of the muscle to the surrounding connective tissue. Zasp is required to assemble the latter and regulate the former adhesion site. Without Zasp the internal, highly repetitive muscle structures also fail to assemble. We analyze Zasp using an array of cell biological and genetic techniques to learn more about muscle attachment and muscle fiber assembly in the fruit fly Drosophila. Zasp is highly conserved in humans, and we already know that humans with mutations in the protein corresponding to Zasp develop cardiomyopathy, which eventually results in heart failure. Investigating Zasp in a simple model organism will therefore increase our understanding of muscle diseases and basic muscle biology.