Dystrobrevin- and dystrophin-like mutants display similar phenotypes in the nematode Caenorhabditis elegans

Abstract

Dystrophin, the protein disrupted in Duchenne muscular dystrophy, forms a transmembrane complex with dystrophin-associated proteins. Dystrobrevins, proteins showing homology to the C-terminal end of dystrophin, and whose function is unknown, are part of the dystrophin complex. We report here that, in the nematode Caenorhabditis elegans, animals carrying mutations in either the dystrophin-like gene dys-1 or the dystrobrevin-like gene dyb-1 display similar behavioral and pharmacological phenotypes consistent with an alteration of cholinergic signalling. These findings suggest that: (1) dystrobrevin and dystrophin are functionally related and (2) their disruption impairs cholinergic signalling.

Interaction of α-Catulin with Dystrobrevin Contributes to Integrity of Dystrophin Complex in Muscle

“…DYB-1 is highly conserved from C. elegans to humans (24). Mutations in dyb-1 cause the head-bending phenotype, which is shared by other C. elegans DAPC mutants (25). Similar to mammalian ␣-dystrobrevin, DYB-1 is reported to interact with DYS-1 and STN-1, an ␣/␤-syntrophin homolog (11).…”

Development, structure, and maintenance of C. elegans body wall muscle

“…No sarcospan counterpart was found (Grisoni et al, 2002;our unpublished results). DYS-1 was shown to interact with DYB-1 and STN-1 suggesting that a DGC may exist in C. elegans (Gieseler et al, 1999a;Gieseler et al, 1999b;Grisoni et al, 2003). In addition, mutation or RNAi mediated gene knock down led to a dys-1 phenotype for some of the DGC ortholog encoding genes: dyb-1, stn-1, stn-2, sgn-1, and sgca-1 (Gieseler et al, 1999a;Grisoni et al, 2002;Grisoni et al, 2003;Zhou et al, 2008;our unpublished observations).…”

“…DYS-1 was shown to interact with DYB-1 and STN-1 suggesting that a DGC may exist in C. elegans (Gieseler et al, 1999a;Gieseler et al, 1999b;Grisoni et al, 2003). In addition, mutation or RNAi mediated gene knock down led to a dys-1 phenotype for some of the DGC ortholog encoding genes: dyb-1, stn-1, stn-2, sgn-1, and sgca-1 (Gieseler et al, 1999a;Grisoni et al, 2002;Grisoni et al, 2003;Zhou et al, 2008;our unpublished observations). Mutations in the dgn-1 gene lead to different phenotypes and the gene is not expressed in muscle (Johnson et al, 2006), thus dgn-1 function is not linked to dys-1.…”

C. elegans models of neuromuscular diseases expedite translational research

“…proteins, and retains the ability to bind to DYS-1 in vitro, suggesting potential conservation of function [35,40]. DYB-1 is expressed from late embryogenesis to adulthood in most neurons and the same muscles as DYS-1, with additional weaker expression in intestinal muscle [36].…”