Project 443270

Muscles contain a highly regular, subcellular assembly of proteins that enable contractility. These huge molecular machines are called myofibrils and we aim to understand how they are built during development, and how different proteins are arranged withing myofibrils to contribute to a fully functional muscle. Contractility is mediated by two different filaments, actin and myosin, that slide past each other. Myosin filaments are anchored at the M-line and actin filaments are anchored at the Z-disc. Our work focuses on the Z-disc proteins of the Zasp family. They play a crucial role in assembly, growth and growth termination of Z-discs by interacting with several other important proteins, in particular actin and the actin cross-linker actinin. We will address three questions: what is the outcome when all Zasp family proteins are removed? This will give critical insight to the redundant core function of Zasp proteins. What is the role of actin- versus actinin-binding? This will tell us about the order of events in muscle assembly and about the final position of Zasp proteins within the Z-disc. And finally, how does Zasp self-interaction initiate and terminate Z-disc and thereby muscle growth? This will help us to better understand Z-disc, but also pathological aggregate formation, which is an important aspect of muscle disorders. This work is done in the Drosophila model system, but human Zasp proteins are closely related, and we will confirm our results with human Zasp proteins.