ヨシナ　サワコ   Yoshina Sawako   吉名　佐和子    所属   医学部 医学科    職種   講師
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),pp.e0133966
著者・共著者	Yoshina Sawako, Mitani Shohei
担当区分	筆頭著者
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