Our laboratory is interested in the formation and function of muscle in the free-living nematode C. elegans. Muscle sarcomere assembly is a highly orchestrated affair involving several proteins. The steps involved in initiating the correct placement of sarcomere substructures is poorly understood. Using mutants in Caenorhabditis elegans we are attempting to dissect the various steps in this process. One interpretation of the current data is that assembly of sarcomeres initiates at the plasma membrane and involves proteins within muscle and within the extracellular matrix.
Studies on muscle mutants with defects in either thick or thin filament components suggests these components do not regulate sarcomere assembly. Recent studies implicate the dense body, the nematode analog of a vertebrate Z-line, as a key component regulating sarcomere initiation, length and orientation. Mutations in the unc-52 gene affect this structure and consequently sarcomere assembly. We have shown that theunc-52 gene encodes a basement membrane proteoglycan similar to vertebrate perlecan. The UNC-52 protein is a component of the extracellular matrix (ECM) underlying all muscle and is concentrated under the transmembrane integrin complexes which anchor muscle sarcomeres. Our current studies are directed at determining how nematode perlecan and other components of the ECM interact with muscle constituents to regulate muscle sarcomere assembly. In collaboration with other laboratories we have shown in recent years that the muscle cell proteins UNC-112, UNC-97/PINCH, PAT-4/ILK and integrin are all essential for myofilament assembly.