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Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion
Kai Liu,Youli Jian,Xiaojuan Sun,Chengkui Yang,Zhiyang Gao,Zhili Zhang,Xuezhao Liu,Yang Li,Jing Xu,Yudong Jing,Shohei Mitani,Sudan He,and Chonglin Yang
The Journal of Cell Biology
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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论文编号: |
DOI:10.1083/jcb.201506081 |
论文题目: |
Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
英文论文题目: |
Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
第一作者: |
Kai Liu,Youli Jian,Xiaojuan Sun,Chengkui Yang,Zhiyang Gao,Zhili Zhang,Xuezhao Liu,Yang Li,Jing Xu,Yudong Jing,Shohei Mitani,Sudan He,and Chonglin Yang |
英文第一作者: |
Kai Liu,Youli Jian,Xiaojuan Sun,Chengkui Yang,Zhiyang Gao,Zhili Zhang,Xuezhao Liu,Yang Li,Jing Xu,Yudong Jing,Shohei Mitani,Sudan He,and Chonglin Yang |
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2016-01-19 |
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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. |
英文摘要: |
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. |
刊物名称: |
The Journal of Cell Biology |
英文刊物名称: |
The Journal of Cell Biology |
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其它备注: |
Kai Liu,Youli Jian,Xiaojuan Sun,Chengkui Yang,Zhiyang Gao,Zhili Zhang,Xuezhao Liu,Yang Li,Jing Xu,Yudong Jing,Shohei Mitani,Sudan He,and Chonglin Yang. Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion. The Journal of Cell Biology. DOI:10.1083/jcb.201506081 |
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