Co-occurrence of tetraspanin and ROS generators: Conservation in protein cross-linking and other developmental processes

The nematode exoskeleton, commonly called the cuticle, is a highly structured extracellular matrix mainly composed of collagen. Secreted collagen molecules from the underlying epidermal cells are cross-linked via their tyrosyl residues. Reactive oxygen species (ROS) are required for the cross-linking reaction to produce tyrosyl radicals. The conserved ROS generator enzyme in C. elegans, BLI-3/CeDUOX1, a homolog of dual oxidases (DUOXs), is responsible for production of hydrogen peroxide. The ROS generation system must be properly controlled since ROS are highly reactive molecules that irreversibly inhibit the functions of cellular components such as nucleic acids and proteins. We recently reported that the ROS generation system directed by BLI-3 requires the tetraspanin protein, TSP-15. Herein we outline the process of cuticle development with a focus on the molecular roles of TSP-15 in the BLI-3 system. We also propose the co-occurrence of tetraspanin and ROS generators by convergent evolution.