Caenorhabditis elegans ADAMTS ADT-2 regulates body size and cuticle collagen organization

The regulation of body size is a fundamental feature of animals critical to their survival and fitness, yet its underlying mechanisms remain poorly understood. In C. elegans, the DBL-1 signaling pathway plays a major role in growth control. The mechanisms by which other pathways regulate body size function, however, are less well understood. To identify additional genes involved in body size regulation, a genetic screen for small mutants was previously performed. One of the genes identified in that screen was sma-21. I now demonstrate that sma-21 encodes ADT-2, a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted metalloproteases. ADAMTS proteins are believed to remodel the extracellular matrix (ECM) and may modulate the activity of extracellular signals. Genetic interactions suggest that ADT-2 acts in parallel with known size regulatory pathways. I further demonstrate that ADT-2 activity is required for normal cuticle collagen fibril organization and adt-2 regulatory sequences drive expression in glial-like cells. ADT-2::GFP fusion protein is localized in the alae and the annuli of the cuticle. We therefore show that ADT-2 is secreted into the cuticle where it may act to proteolytically process secreted collagen or other ECM molecules required for normal cuticle structure and body size.