| Summary: | Unc-112 and dim-1 are a pair of interacting genes that are required for myofilament lattice
assembly and maintenance in the nematode, Caenorhabdidtis elegans. The unc-112 gene
encodes a novel protein localized to attachment structures that are responsible for anchoring the
myofilament lattice to the muscle cell membrane and underlying body wall layers. Loss of UNC-
112 results in the failure of myofilament lattice assembly and lethality. Animals homozygous for
the missense mutation unc-112 (r367), on the other hand, survive to adulthood but are paralyzed
and have severely disorganized body wall muscle. Mutations in the dim-1 gene can suppress the
phenotypic defects associated with unc-112 (r367). Animals homozygous for both dim-1 and
unc-112 (r367) display wild type movement and have relatively well organized body wall muscle.
Animals homozygous for the dim-1 mutation alone display mildly disorganized muscle, thus the
dim-1 gene is required for maintaining muscle stability.
The dim-1 gene encodes a 325 amino acid protein that constitutes three immunoglobulin
repeats that are most similar to the intracellular muscle proteins, titin and twitchin.
Immunofluorescence analysis revealed that DIM-1 is expressed in body wall muscle in a pattern
reminiscent of myofilament associated proteins. Preliminary results suggest DIM-1 may
associate with actin containing thin filaments. The disorganized muscle phenotype of dim-1
mutants and the localization of its gene product suggest that DIM-1 maintains the integrity of the
myofilament lattice through the stabilization of thin filaments.
Results presented in this thesis suggest that the suppression of unc-112 (r367) by dim-1 is
indirect. First, sequence alterations for eight dim-1 alleles have been identified all of which result
in the loss of the dim-1 gene product. Thus, the absence of DIM-1 results in the suppression of
unc-112 (r367). Second, DIM-1 is not required for localization of UNC-112 to attachment
structures and third, the DIM-1 protein is localized to myofilaments rather than attachment
structures. These results indicate that the genetic interaction between dim-1 and unc-112 is not
due to a direct interaction between their gene products. Rather, suppression of unc-112 appears
to result from a change in the overall stability of the myofilament lattice caused by the loss of
dim-1. This change may allow the altered r367 protein to maintain the integrity of the
myofilament lattice. === Science, Faculty of === Zoology, Department of === Graduate
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