The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell-matrix adhesion structures required for integrin localization in the muscle cell membrane

Embryos homozygous for mutations in the unc-52, pat-2, pat-3, and unc-112 g enes of C. elegans exhibit a similar Pat phenotype, Myosin and actin are no t organized into sarcomeres in the body wall muscle cells of these mutants, and dense body and M-line components fail to assemble. The unc-52 (perleca n), pat-2 (alpha-integrin), and pat-3 (P-integrin) genes encode ECM or tran smembrane proteins found at the cell-matrix adhesion sites of both dense bo dies and M-lines. This study describes the identification of the unc-112 ge ne product, a novel, membrane-associated, intracellular protein that coloca lizes with integrin at cell-matrix adhesion complexes. The 720-amino acid U NC-112 protein is homologous to Mig-2, a human protein of unknown function. These two proteins share a region of homology with talin and members of th e FERM super-family of proteins. We have determined that a functional UNC-112:: GFP fusion protein colocaliz es with PAT-3/beta-integrin in both adult and embryonic body wall muscle. W e also have determined that UNC-112 is required to organize PAT-3/beta-inte grin after it is integrated into the basal cell membrane, but is not requir ed to organize UNC-52/perlecan in the basement membrane, nor for DEB-1/vinc ulin to localize with PAT-3/beta-integrin, Furthermore, UNC-112 requires th e presence of UNC-52/perlecan and PAT-YP-integrin, but not DEB-1/vinculin t o become localized to the muscle cell membrane.