2. Academic Validation
  3. Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion

Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion

  • J Cell Biol. 2016 Jan 18;212(2):181-98. doi: 10.1083/jcb.201506081.
Kai Liu 1,  Youli Jian 2,  Xiaojuan Sun 2,  Chengkui Yang 3,  Zhiyang Gao 2,  Zhili Zhang 3,  Xuezhao Liu 1,  Yang Li 2,  Jing Xu 2,  Yudong Jing 2,  Shohei Mitani 4,  Sudan He 3,  Chonglin Yang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. Beijing 100101, China Graduate University of Chinese Academy of Sciences, Beijing 100109, China.
  • 2 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. Beijing 100101, China.
  • 3 Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital and Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215123, China.
  • 4 Department of Physiology, School of Medicine and Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Shinjuku-ku, Tokyo 162-0054, Japan.
  • 5 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. Beijing 100101, China [email protected].
PMID: 26783301 DOI: 10.1083/jcb.201506081
Abstract

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.

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