Dissecting the role of ALP-1 and EAT-1 proteins in regulation of muscle structure and function

The purpose of this dissertation is to define how muscle cells maintain their contractile machinery and how a rhythmic muscle contraction is regulated. These studies employed C. elegans as a model system to characterize pathways required for normal muscle structure and function. With easy manipulation and a wide variety of genetic tools, C. elegans is a powerful and efficient system to study gene function and to dissect underlying molecular mechanisms. In the first part of this dissertation, Z-disc-associated muscle proteins of the ALPEnigma family were characterized. The alp-1 gene in C. elegans encodes multiple ALPEnigma proteins. The ALP-1 proteins are broadly expressed at actin-anchorage sites, and play a role in maintaining actin filament organization within muscles. Genetic analysis revealed that ALP-1 and alpha-actinin act together to support the integrity of actin cytoarchitecture. The second part of this dissertation is focused on the characterization of the eat-1 gene in C. elegans. Mutations in eat-1 cause defects in the rhythmic contraction of the pharynx, an organ in the C. elegans digestive tract that is comprised of muscle, neuronal and epithelial cells, eat-1 encodes adenosine kinase, an evolutionarily conserved enzyme that catalyzes adenosine to adenosine monophosphate. Molecular and genetic studies showed that EAT-1 acts noncell autonomously and modulates adenosine receptormediated signaling to regulate pharyngeal muscle contraction. The studies reveal the important role of ALP-Enigma proteins in maintaining muscle structural integrity, and of adenosine kinase in regulating rhythmic muscle contraction, enhancing our knowledge of how muscle cells maintain their structure and contract properly.