The Immunoglobulin Domain of SISS-1/EGF is Required for its Function

Epidermal growth factor (EGF) signaling plays roles in development and physiology across the animal kingdom. In the nematode <i>C. elegans</i> , a single EGF receptor (EGFR) and two EGF family ligands have been characterized. LIN-3 /EGF is required for a variety of developmental processes as well as ovulation, and SISS-1 /EGF promotes a damage-responsive quiescent state known as stress-induced sleep. Like all EGF family ligands, SISS-1 and LIN-3 are produced as transmembrane proteins with an extracellular EGF-like domain, known for its function in receptor binding. The ectodomain of SISS-1 , but not of LIN-3 , also contains an Immunoglobulin-like (Ig) domain, putting it into a class of Ig-EGFs that includes <i>Drosophila</i> Vein and certain vertebrate Neuregulins. The function of the Ig domain within Ig-EGFs appears to vary. Here, we investigate the SISS-1 Ig domain and show that it is essential for stress-induced sleep.