Loss of dystrophin and the microtubule-binding protein ELP-1 causes progressive paralysis and death of adult C. elegans

Abstract

EMAP-like proteins (ELPs) are conserved microtubule-binding proteins that function during cell division and in the behavior of post-mitotic cells. In C. 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.