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WDR91 is A Rab7 Effector Required for Neuronal Eevelopment
Kai Liu, Ruxiao Xing, Youli Jian, Zhiyang Gao, Xinli Ma, Xiaojuan Sun, Yang Li, Meng Xu, Xin Wang, Yudong Jing, Weixiang Guo, Chonglin Yang
The Journal of Cell Biology
Abstract
Early-to-late endosome conversion, which is essential for delivery of endosomal cargoes to lysosomes, requires switching of early endosome–specific Rab5 and PtdIns3P to late endosome–specific Rab7 and PtdIns(3,5)P2. In this study, we identify the WD40-repeat protein WDR91 as a Rab7 effector that couples Rab switching with PtdIns3P down-regulation on endosomes. Loss of WDR91 greatly increases endosomal PtdIns3P levels, arresting endosomes at an intermediate stage and blocking endosomal–lysosomal trafficking. WDR91 is recruited to endosomes by interacting with active guanosine triphosophate–Rab7 and inhibits Rab7-associated phosphatidylinositol 3-kinase activity. In mice, global Wdr91 knockout causes neonatal death, whereas brain-specific Wdr91 inactivation impairs brain development and causes postnatal death. Mouse neurons lacking Wdr91 accumulate giant intermediate endosomes and exhibit reduced neurite length and complexity. These phenotypes are rescued by WDR91 but not WDR91 mutants that cannot interact with Rab7. Thus, WDR91 serves as a Rab7 effector that is essential for neuronal development by facilitating endosome conversion in the endosome–lysosome pathway.
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论文编号: |
DOI:10.1083/jcb.201705151 |
论文题目: |
WDR91 is A Rab7 Effector Required for Neuronal Eevelopment |
英文论文题目: |
WDR91 is A Rab7 Effector Required for Neuronal Eevelopment |
第一作者: |
Kai Liu, Ruxiao Xing, Youli Jian, Zhiyang Gao, Xinli Ma, Xiaojuan Sun, Yang Li, Meng Xu, Xin Wang, Yudong Jing, Weixiang Guo, Chonglin Yang |
英文第一作者: |
Kai Liu, Ruxiao Xing, Youli Jian, Zhiyang Gao, Xinli Ma, Xiaojuan Sun, Yang Li, Meng Xu, Xin Wang, Yudong Jing, Weixiang Guo, Chonglin Yang |
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2017-10-10 |
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Early-to-late endosome conversion, which is essential for delivery of endosomal cargoes to lysosomes, requires switching of early endosome–specific Rab5 and PtdIns3P to late endosome–specific Rab7 and PtdIns(3,5)P2. In this study, we identify the WD40-repeat protein WDR91 as a Rab7 effector that couples Rab switching with PtdIns3P down-regulation on endosomes. Loss of WDR91 greatly increases endosomal PtdIns3P levels, arresting endosomes at an intermediate stage and blocking endosomal–lysosomal trafficking. WDR91 is recruited to endosomes by interacting with active guanosine triphosophate–Rab7 and inhibits Rab7-associated phosphatidylinositol 3-kinase activity. In mice, global Wdr91 knockout causes neonatal death, whereas brain-specific Wdr91 inactivation impairs brain development and causes postnatal death. Mouse neurons lacking Wdr91 accumulate giant intermediate endosomes and exhibit reduced neurite length and complexity. These phenotypes are rescued by WDR91 but not WDR91 mutants that cannot interact with Rab7. Thus, WDR91 serves as a Rab7 effector that is essential for neuronal development by facilitating endosome conversion in the endosome–lysosome pathway. |
英文摘要: |
Early-to-late endosome conversion, which is essential for delivery of endosomal cargoes to lysosomes, requires switching of early endosome–specific Rab5 and PtdIns3P to late endosome–specific Rab7 and PtdIns(3,5)P2. In this study, we identify the WD40-repeat protein WDR91 as a Rab7 effector that couples Rab switching with PtdIns3P down-regulation on endosomes. Loss of WDR91 greatly increases endosomal PtdIns3P levels, arresting endosomes at an intermediate stage and blocking endosomal–lysosomal trafficking. WDR91 is recruited to endosomes by interacting with active guanosine triphosophate–Rab7 and inhibits Rab7-associated phosphatidylinositol 3-kinase activity. In mice, global Wdr91 knockout causes neonatal death, whereas brain-specific Wdr91 inactivation impairs brain development and causes postnatal death. Mouse neurons lacking Wdr91 accumulate giant intermediate endosomes and exhibit reduced neurite length and complexity. These phenotypes are rescued by WDR91 but not WDR91 mutants that cannot interact with Rab7. Thus, WDR91 serves as a Rab7 effector that is essential for neuronal development by facilitating endosome conversion in the endosome–lysosome pathway. |
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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, Ruxiao Xing, Youli Jian, Zhiyang Gao, Xinli Ma, Xiaojuan Sun, Yang Li, Meng Xu, Xin Wang, Yudong Jing, Weixiang Guo, Chonglin Yang. WDR91 is A Rab7 Effector Required for Neuronal Eevelopment. The Journal of Cell Biology. DOI:10.1083/jcb.201705151. |
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