title: DYC-1, a protein functionally linked to dystrophin in Caenorhabditis elegans is associated with the dense body, where it interacts with the muscle LIM domain protein ZYX-1.
abstract: In Caenorhabditis elegans, mutations of the dystrophin homologue, dys-1, produce a peculiar behavioral phenotype (hyperactivity and a tendency to hypercontract). In a sensitized genetic background, dys-1 mutations also lead to muscle necrosis. The dyc-1 gene was previously identified in a genetic screen because its mutation leads to the same phenotype as dys-1, suggesting that the two genes are functionally linked. Here, we report the detailed characterization of the dyc-1 gene. dyc-1 encodes two isoforms, which are expressed in neurons and muscles. Isoform-specific RNAi experiments show that the absence of the muscle isoform, and not that of the neuronal isoform, is responsible for the dyc-1 mutant phenotype. In the sarcomere, the DYC-1 protein is localized at the edges of the dense body, the nematode muscle adhesion structure where actin filaments are anchored and linked to the sarcolemma. In yeast two-hybrid assays, DYC-1 interacts with ZYX-1, the homologue of the vertebrate focal adhesion LIM domain protein zyxin. ZYX-1 localizes at dense bodies and M-lines as well as in the nucleus of C. elegans striated muscles. The DYC-1 protein possesses a highly conserved 19 amino acid sequence, which is involved in the interaction with ZYX-1 and which is sufficient for addressing DYC-1 to the dense body. Altogether our findings indicate that DYC-1 may be involved in dense body function and stability. This, taken together with the functional link between the C. elegans DYC-1 and DYS-1 proteins, furthermore suggests a requirement of dystrophin function at this structure. As the dense body shares functional similarity with both the vertebrate Z-disk and the costamere, we therefore postulate that disruption of muscle cell adhesion structures might be the primary event of muscle degeneration occurring in the absence of dystrophin, in C. elegans as well as vertebrates.
authors: Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5534, Centre de Génétique Moléculaire et Cellulaire, Bâtiment Mendel, Villeurbanne, F-69622, France.
authors: Claire
authors: C
authors: Lecroisey
authors: Edwige
authors: E
authors: Martin
authors: Marie-Christine
authors: MC
authors: Mariol
authors: Laure
authors: L
authors: Granger
authors: Yannick
authors: Y
authors: Schwab
authors: Michel
authors: M
authors: Labouesse
authors: Laurent
authors: L
authors: Ségalat
authors: Kathrin
authors: K
authors: Gieseler
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D022083:Cytoplasmic Structures / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism*; D005786:Gene Expression Regulation; D060588:LIM Domain Proteins; D016253:Microscopy, Immunoelectron; D008954:Models, Biological; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D060589:Zyxin
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C532813:DYC-1 protein, C elegans; D016189:Dystrophin; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C532814:ZYX-1 protein, C elegans; D060589:Zyxin; C090114:cysteine and glycine-rich protein 3; C406103:dys-1 protein, C elegans