Embryos homozygous for null mutations in the
unc-112 gene exhibit a Pat terminal phenotype. They arrest at the two-fold stage of embryogenesis and have severely disorganized body wall muscle. In contrast, animals carrying the
r367 allele are viable, although they do have disorganized body wall muscle and are paralyzed as adults. We have isolated several extragenic suppressors of
unc-112(
r367) by selecting well moving animals from the progeny of mutagenized hermaphrodites. All of the suppressor mutations characterized are alleles of the
dim-1 (disorganized muscle) gene positioned between
dpy-7 and
dpy-6 on the X chromosome. These alleles are null mutations and are able to suppress the paralyzed phenotype of
unc-112(
r367) when either heterozygous or homozygous. Thus, reduction or loss of
dim-1 gene function results in suppression of
unc-112(
r367) . Hermaphrodites homozygous for a
dim-1 mutation alone exhibit wild-type movement, however, the body wall muscle appears disorganized when viewed under polarized light. The
dim-1 gene encodes a novel 640 amino acid protein that is presumably required for myofilament lattice stability in the body wall muscle. We have identified the sequence alterations for three
dim-1 alleles, and are in the process of generating a polyclonal antibody to the DIM-1 protein. The
unc-112 gene corresponds to the C47E8.7 ORF, and encodes a novel, membrane associated, intracellular protein that co-localizes with perlecan and integrin at muscle cell dense bodies and M-lines. The 720 amino acid UNC-112 protein is most similar to a human protein of unknown function called Mig-2 (Wicks et al., 1994, J. Cell Sci. 107:227), but also shares a short, ~50 amino acid region of homology with Talin, Band 4.1 and Ezrin that may be important for attachment to the plasma membrane. Our analysis of embryos homozygous for
unc-112 null alleles reveals that this protein is required for the proper localization of PAT-3/integrin in the muscle cell membrane. In contrast, the absence of the UNC-112 protein has no effect on the localization of UNC-52/perlecan in the ECM.