In vertebrates the matrix receptor dystroglycan provides a transmembrane linkage of basement membrane components such as laminin to cytoskeletal and signaling networks via a cytoplasmic dystrophin associated protein (DAP) complex containing dystrophin, dystrobrevin and syntrophin. Dystroglycan-matrix attachment is important in muscle, epithelial and glial tissue. We are examining the functions of the dystroglycan homolog DGN-1. Expression of
dgn-1 is seen throughout development in epithelia in the pharynx, gonad, vulva, rectum, excretory cell and hypodermis, as well as in a variety of neurons. DGN-1 localizes to cell surfaces apposed to a basement membrane, consistent with a conserved role as a matrix receptor. A null mutant of
dgn-1 is viable but sterile due to early failure of gonad epithelialization, and has defects in the vulval epithelium resulting in protrusion and herniation. Excretory cell processes often fail to extend in
dgn-1(0),and there are mild defects in the guidance of motoneuron axons. Unlike its vertebrate homolog, DGN-1 is not detected in muscle, and disruption of muscle structure or function are not seen in the mutant. The gonad phenotype of
dgn-1(0) is similar to that of laminin
epi-1 mutants, suggesting a conservation of the laminin-dystroglycan interaction. EPI-1 localizes to basement membranes around the gonad and other tissues, and
epi-1 mutants have additional defects in the vulval epithelium and hypodermis, excretory cell processes, and neural guidance and organization (Hwang et al, Development 130:3343, 2003). The range and severity of
epi-1 mutant defects indicate that DGN-1 is not the sole mediator of EPI-1 function. In contrast to the gonad and other morphological defects in
dgn-1(0), mutants in the worm DAP homologs DYS-1/dystrophin, DYB-1/dystrobrevin and STN-1/syntrophin show a hypercontraction of the head musculature that is not observed in
dgn-1(0). The DAP mutants and
dgn-1(0) are both hyperactive, but analysis of double mutants suggests that
dgn-1 is not acting through the same mechanism as the DAP components. Null
dgn-1 mutants show additional behavioral phenotypes not seen in the DAP mutants. Prevous studies indicate that the worm DAP functions in muscle, where
dgn-1 is not expressed. DGN-1 function is thus largely independent of the conserved dystrophin complex, in contrast to the critical co-function of dystroglycan with this complex in vertebrates. To identify the functional partners of DGN-1, we are performing both random and targeted screens for genes interacting with
dgn-1. Analysis of a suppressor of the
dgn-1 null mutant isolated in one such screen should yield insight into DGN-1 function.