The C. elegans HGF/plasminogen-like protein SVH-1 has protease-dependent and -independent functions

Hepatocyte growth factor (HGF) and fibrinolytic serine protease plasminogen may have evolved from a common ancestor in vertebrates. This has been hard to ascertain, as no ancestral form has been identified in other lineages. In Caenorhabditis elegans, an HGF/plasminogen-like protein SVH-1 regulates axon regeneration via the HGF receptor homolog SVH-2. In this study, we report that both the svh-1 and svh-2 genes are conserved in many invertebrates. We also show that SVH-1 has an additional function, independent of SVH-2, which controls larval growth. SVH-1 protease activity is essential for larval growth, but not for axon regeneration. Deletion of svh-1 causes abnormal accumulation of FBL-1 protein, an extracellular matrix (ECM) component fibulin, around the pharynx, and this growth defect is partially suppressed by FBL-1 depletion. These results suggest that SVH-1 acts as both a growth factor and a protease, and they also provide insights into the evolution of HGF/plasminogen in animals.