Muscle contraction is accomplished by the action of a highly ordered filament system, called the contractile apparatus. The long-term goal of this project is to understand at the molecular level the mechanisms by which the cell assembles this precisely patterned structure. This research examines the physiological role of the newly identified protein UNC-82, which is required for proper formation of thick filaments and their incorporation into the contractile apparatus in the nematode, C. elegans. To define the interaction of UNC-82 with known components of the contractile apparatus, antibody probes specific for UNC-82 protein will be generated and used to determine the subcellular localization of UNC-82 in the muscle cells of normal and mutant worm strains. Genetic screens and biochemical tests will be used to define regions of the UNC-82 protein that are important for its function and to identify other proteins that interact with UNC-82. The experiments will clarify potential regulatory roles for UNC-82 in the formation of muscle contractile apparatus.

Some of the same proteins required for proper establishment of the contractile apparatus in muscle are also found in other tissues. In C. elegans, UNC-82 is also found in neurons, and in skin, where it is associated with a distinct filament system that maintains the structural integrity of the epidermis. Although the organization of filaments in these other cells is not as highly ordered as in muscle, non-muscle cell function also depends upon the correct formation and maintenance of structural elements at precise locations within the cell. Therefore, this project will further our understanding of the genesis of cellular organization in a large number of tissue types. The results should also be applicable to our understanding of filament structures in other organisms, because sequence information from genome projects has identified proteins with similarity to UNC-82 in other species. Much of the research will be done by undergraduate students, who will receive valuable research experience.

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Washington University School of Medicine
Saint Louis
United States
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