title: The C. elegans HGF/plasminogen-like protein SVH-1 has protease-dependent and -independent functions.
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.
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan. Electronic address: i45556a@cc.nagoya-u.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hisamoto
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan. Electronic address: g44177a@nucc.cc.nagoya-u.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005769:Gastrointestinal Motility; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D007814:Larva / Q000201:enzymology / Q000254:growth & development; D009119:Muscle Contraction; D009928:Organ Specificity; D010614:Pharynx / Q000502:physiology; D010958:Plasminogen / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C066855:HGF protein, human; D036341:Intercellular Signaling Peptides and Proteins; C572121:SVH-1 protein, C elegans; C060820:fibulin; D017228:Hepatocyte Growth Factor; D010958:Plasminogen