title: Loss of C. elegans GON-1, an ADAMTS9 Homolog, Decreases Secretion Resulting in Altered Lifespan and Dauer Formation.
abstract: ADAMTS9 is a metalloprotease that cleaves components of the extracellular matrix and is also implicated in transport from the endoplasmic reticulum (ER) to the Golgi. It has been reported that an ADAMTS9 gene variant is associated with type 2 diabetes. The underlying pathology of type 2 diabetes is insulin resistance and beta-cell dysfunction. However, the molecular mechanisms underlying ADAMTS9 function in beta cells and peripheral tissues are unknown. We show that loss of C. elegans GON-1, an ADAMTS9 homolog, alters lifespan and dauer formation. GON-1 loss impairs secretion of proteins such as insulin orthologs and TGF-beta, and additionally impacts insulin/IGF-1 signaling in peripheral tissues. The function of the GON domain, but not the protease domain, is essential for normal lifespan and dauer formation in these scenarios. We conclude that the GON domain is critical for ADAMTS9/GON-1 function across species, which should help the understanding of type 2 diabetes in humans.
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, 162-8666, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Yoshina
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, 162-8666, Japan; Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS), Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D007814:Larva / Q000254:growth & development* / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D051722:ADAM Proteins; C119674:GON-1 protein, C elegans; D008666:Metalloendopeptidases