Loss of dystrophin and the microtubule-binding protein ELP-1 causes progressive paralysis and death of adult C. elegans.
EMAP-like proteins (ELPs) are conserved microtubule-binding proteins that function during cell division and in the behavior of post-mitotic cells. In Caenorhabditis elegans, ELP-1 is broadly expressed in many cells and tissues including the touch receptor neurons and body wall muscle. Within muscle, ELP-1 is associated with a microtubule network that is closely opposed to the integrin-based adhesion sites called dense bodies. To examine ELP-1 function, we utilized an elp-1 RNA interference assay and screened for synthetic interactions with mutated adhesion site proteins. We reveal a synthetic lethal relationship between ELP-1 and the dystrophin-like protein, DYS-1. Reduction of ELP-1 in a dystrophin [dys-1(cx18)] mutant results in adult animals with motility defects, splayed and hypercontracted muscle with altered cholinergic signaling. Worms fill with vesicles, become flaccid, and die. We conclude that ELP-1 is a genetic modifier of a C. elegans model of muscular dystrophy.
Hueston
Jennifer L
JL
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045-7534, USA.
Suprenant
Kathy A
KA
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017238:Genes, Helminth; D005804:Genes, Lethal; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D009137:Muscular Dystrophy, Animal / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology; D013696:Temperature
D029742:Caenorhabditis elegans Proteins; D016189:Dystrophin; C539475:ELP-1 protein, C elegans; D008869:Microtubule-Associated Proteins; C406103:dys-1 protein, C elegans; D000109:Acetylcholine