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

Cell Rep. 2014 Dec 11;9(5):1628-1634. doi: 10.1016/j.celrep.2014.10.056. Epub 2014 Nov 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / physiology*
  • Calcium-Binding Proteins / metabolism
  • Conserved Sequence
  • Evolution, Molecular
  • Gastrointestinal Motility
  • Gene Expression
  • Hepatocyte Growth Factor / genetics
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Larva / enzymology
  • Larva / growth & development
  • Muscle Contraction
  • Organ Specificity
  • Pharynx / physiology
  • Plasminogen / genetics

Substances

  • Caenorhabditis elegans Proteins
  • Calcium-Binding Proteins
  • HGF protein, human
  • Intercellular Signaling Peptides and Proteins
  • SVH-1 protein, C elegans
  • fibulin
  • Hepatocyte Growth Factor
  • Plasminogen