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The role of the dim-1 gene in muscle maintenance and stability in Caenorhabditis elegans

University of British Columbia

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.

Thesis/Dissertation

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2009-07-06

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http://hdl.handle.net/2429/10205

Zoology

University of British Columbia

UBCV

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