RRC ID 45670
Author Yoshina S, Mitani S.
Title Loss of C. elegans GON-1, an ADAMTS9 Homolog, Decreases Secretion Resulting in Altered Lifespan and Dauer Formation.
Journal PLoS One
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.
Volume 10(7)
Pages e0133966
Published 2015-1-1
DOI 10.1371/journal.pone.0133966
PII PONE-D-15-01195
PMID 26218657
PMC PMC4517882
MeSH ADAM Proteins / genetics ADAM Proteins / metabolism* Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / growth & development* Animals, Genetically Modified / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Endoplasmic Reticulum / metabolism Golgi Apparatus / metabolism Insulin / metabolism* Insulin Secretion Insulin-Secreting Cells / cytology Insulin-Secreting Cells / metabolism Larva / growth & development* Larva / metabolism Longevity / physiology* Metalloendopeptidases / genetics Metalloendopeptidases / metabolism*
IF 2.74
Times Cited 4
C.elegans tm3146 tm1907 tm2308