The nematode Caenorhabditis elegans has a homologue of dystrophin (
dys-1), the protein mutated in patients suffering from Duchenne muscular dystrophy. In a forward genetics approach (see poster of Grisoni et al.), we isolated mutations in other genes with
dys-1-like phenotypes. One of these genes corresponds to the C. elegans dystrobrevin gene (
dyb-1), which encodes a protein that binds dystrophin directly through coiled-coil domains. The forward genetics approach also made it possible to isolate a novel gene functionally related to dystrophin,
dyc-1. The DYC-1 protein is not homologous to any known mammalian proteins, but comprises two regions of similarity to CAPON, a nNOS-binding protein. Like DYS-1 and DYB-1, DYC-1 contains a putative coiled-coil domain. A search for protein motifs with the Prosite program reveals a high number of putative PKA- and PKC-dependent phosphorylation sites in DYC-1. Our data indicate that
dyc-1 has muscular and neuronal isoforms. The muscular isoform is expressed in head muscles, body wall muscles and vulva muscles. A gfp fusion protein with the neuronal isoform stains approximately 20 neurones in the animal. Staining is these neurones appear as dots along the neuronal processes. The nature of these dots has not been identified. Loss-of-function mutations in the
dys-1 or in the
dyc-1 gene do not alter the muscle structure, but make animals hyperactive and slightly hypercontracted. However, the combination of a
dys-1 null mutation or a
dyc-1 null mutation with a weak mutation of
hlh-1, the C. elegans MyoD homologue, results in a time-dependent disorganisation of musculature. The overexpression of
dyc-1 in a
dys-1;
hlh-1 genetic background partially suppresses the muscle phenotype. This observation, as well as the similarity of
dys-1 and
dyc-1 loss-of-function phenotypes suggests that both genes participate in the same physiological function (Gieseler et al., 2000). Using the yeast two-hybrid system, we identified a putative partner of DYC-1: F42G4.3. This protein, which has at least two isoforms, has no known homologues in other species. A preliminary analysis using GFP-reporter gene expression shows that F42G4.3 is expressed in muscles and neurones in a pattern resembling that of
dyc-1 and
dyb-1.