Volume 26, No 5, May 2016

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 26 Issue 5, May 2016: 593-612

ORIGINAL ARTICLES

Numb regulates vesicular docking for homotypic fusion of early endosomes via membrane recruitment of Mon1b

Ximing Shao^1,*, Yi Liu^1,2,7,*, Qian Yu^1,2,*, Zhihao Ding¹, Wenyu Qian^2,3, Lei Zhang¹, Jianchao Zhang¹, Nan Jiang^2,8, Linfei Gui¹, Zhiheng Xu⁵, Yang Hong⁶, Yifan Ma¹, Yanjie Wei¹, Xiaoqing Liu³, Changan Jiang^1,2, Minyan Zhu³, Hongchang Li¹ and Huashun Li^3,4

¹Shenzhen 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
²West 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
³SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200123, China
⁴ATCG Corp, BioBay, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China
⁵State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
⁶Department of Cell Biology & Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
⁷Current address: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
⁸Current address: Department of Biology, University of Washington, Seattle, Washington, USA Correspondence: Hongchang Li, E-mail: hc.li@siat.ac.cn; Huashun Li,(huashunli@tongji.edu.cn)

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.

10.1038/cr.2016.34

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