title: Numb regulates vesicular docking for homotypic fusion of early endosomes via membrane recruitment of Mon1b.
abstract: Numb is an endocytic protein that plays crucial roles in diverse cellular processes such as asymmetric cell division, cell migration and differentiation. However, the molecular mechanism by which Numb regulates endocytic trafficking is poorly understood. Here, we demonstrate that Numb is a docking regulator for homotypic fusion of early endosomes (EEs). Numb depletion causes clustered but unfused EEs, which can be rescued by overexpressing cytosolic Numb 65 and Numb 71 but not plasma membrane-attached Numb 66 or Numb 72. Time-lapse analysis reveals that paired vesicles tend to tether but not fuse with each other in the absence of Numb. We further show that Numb binds to another docking regulator, Mon1b, and is required for the recruitment of cytosolic Mon1b to the EE membrane. Consistent with this, deletion of Mon1b causes similar defects in EE fusion. Our study thus identifies a novel mechanism by which Numb regulates endocytic sorting by mediating EE fusion.
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Ximing
authors.initials: X
authors.lastname: Shao
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.|West China Developmental & Stem Cell Biology Institute, West China Second University Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.|Current address: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.|West China Developmental & Stem Cell Biology Institute, West China Second University Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Ding
authors.affiliation: West China Developmental & Stem Cell Biology Institute, West China Second University Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.|SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200123, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Qian
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: West China Developmental & Stem Cell Biology Institute, West China Second University Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.|Current address: Department of Biology, University of Washington, Seattle, Washington, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Linfei
authors.initials: L
authors.lastname: Gui
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Cell Biology & Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Wei
authors.affiliation: SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200123, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.|West China Developmental & Stem Cell Biology Institute, West China Second University Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Changan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200123, China.
authors.forename: Minyan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Li
authors.affiliation: SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200123, China.|ATCG Corp, BioBay, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
authors.forename: Huashun
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C477373:MON1B protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C113026:NUMB protein, human; D011506:Proteins