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 Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion.
掲載誌名 正式名:The Journal of cell biology
略  称:J Cell Biol
ISSNコード:(1540-8140)0021-9525(Linking)
掲載区分国外
巻・号・頁 212(2),181-98頁
著者・共著者 Liu Kai, Jian Youli, Sun Xiaojuan, Yang Chengkui, Gao Zhiyang, Zhang Zhili, Liu Xuezhao, Li Yang, Xu Jing, Jing Yudong, Mitani Shohei, He Sudan, Yang Chonglin
発行年月 2016/01
概要 Phosphatidylinositol 3-phosphate (PtdIns3P) plays a central role in endosome fusion, recycling, sorting, and early-to-late endosome conversion, but the mechanisms that determine how the correct endosomal PtdIns3P level is achieved remain largely elusive. Here we identify two new factors, SORF-1 and SORF-2, as essential PtdIns3P regulators in Caenorhabditis elegans. Loss of sorf-1 or sorf-2 leads to greatly elevated endosomal PtdIns3P, which drives excessive fusion of early endosomes. sorf-1 and sorf-2 function coordinately with Rab switching genes to inhibit synthesis of PtdIns3P, allowing its turnover for endosome conversion. SORF-1 and SORF-2 act in a complex with BEC-1/Beclin1, and their loss causes elevated activity of the phosphatidylinositol 3-kinase (PI3K) complex. In mammalian cells, inactivation of WDR91 and WDR81, the homologs of SORF-1 and SORF-2, induces Beclin1-dependent enlargement of PtdIns3P-enriched endosomes and defective degradation of epidermal growth factor receptor. WDR91 and WDR81 interact with Beclin1 and inhibit PI3K complex activity. These findings reveal a conserved mechanism that controls appropriate PtdIns3P levels in early-to-late endosome conversion.
DOI 10.1083/jcb.201506081
PMID 26783301