Action of MAM Domain Proteins in the Molting Cycle of Caenorhabditis elegans

Caenorhabditis elegans periodically sheds and remakes its exoskeleton (cuticle) in order to grow. During this molting process, epidermal cells fully renovate local extracellular matrices (ECM) and related cell-ECM and cell-cell attachments. This study investigates the mlt-9 and mam-1 genes, which were previously identified in an RNA interference (RNAi)-based screen for larvae unable to shed cuticles.  Both genes encode annotated secreted proteins with MAM domains, which are characteristic of adhesive molecules. We hypothesized that interactions between the MAM domains of MLT-9 and MAM-1 contribute to dynamic changes in adhesion among epidermal cells and the ECM and are critical for molting. Genetic and cell biological analysis were used to test this hypothesis. Specifically, mlt-9 and mam-1 mutants were examined for defects in the molting process and abnormal development of the epidermal cells that produce the cuticle. Consistent with our model, specific loss-of-function phenotypes and genetic analysis suggest that MLT-9 and MAM-1 regulate cell-matrix adhesion and promote proper development of the epidermis. Additionally, MLT-9 expression was detected in epidermal cells while cuticles are remade. Because the C. elegans exoskeleton is a collagenous ECM similar to human skin and connective tissue, these findings about the regeneration of the nematode exoskeleton will likely apply to vertebrate ECM homeostasis, a critical process for normal development and wound repair.