ミタニ シヨウヘイ   MITANI Shohei
  三谷 昌平
   所属   医学部 医学科
   職種   教授・講座主任
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Loss of C. elegans GON-1, an ADAMTS9 Homolog, Decreases Secretion Resulting in Altered Lifespan and Dauer Formation.
掲載誌名 正式名:PloS one
略  称:PLoS One
ISSNコード:(1932-6203)1932-6203(Linking)
巻・号・頁 10(7),e0133966頁
著者・共著者 Yoshina Sawako, Mitani Shohei
発行年月 2015/07
概要 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.
DOI 10.1371/journal.pone.0133966
PMID 26218657