Calvin College1, Department of Biology, Grand Rapids, MI 49546 Western Michigan University2, Department of Biological Science, Kalamazoo, MI 49008
A number of mutant strains of the small nematode Caenorhabditis elegans display disorganization of the normally highly ordered cytoskeletal network within the body-wall muscle cell’s contractile apparatus. Two of these mutant strains contain point mutations in the unc-82 gene. UNC-82 contains a putative serine-threonine kinase catalytic domain, which is orthologous to the ARK-5 and SNARK human proteins associated with tumor formation. In C. elegans, UNC-82 has been shown to play a role in the maintenance of thick filament and M-line organization. Two recessive, loss-of-function unc-82 mutations exist. The allele e1323 introduces an early stop codon in the kinase domain while e1220 introduces a missense mutation, but produces a full length protein. The former represents a null (complete loss-of-function) mutation, while the latter is a putative kinase-dead mutation. Mutant worms homozygous for the e1220 allele display a less severe phenotype than those homozygous for the e1323 allele. To further investigate the role of UNC-82 in muscle organization and maintenance it is desired to create new unc-82 alleles through ethyl methanesulfonate (EMS) and N-ethyl-N-nitrosourea (ENU) mutagenesis. New alleles will aid in the understanding of the function of UNC-82 and the mechanisms that govern the formation and organization of the muscle cell cytoskeletal network. Insight into the role that UNC-82 plays in C. elegans may further elucidate the function that the orthologous human kinases play in the stress response or tumor formation, as well as any undiscovered role they may play in normal development.
[Abstract (DOC)]