期刊
CELL RESEARCH
卷 26, 期 5, 页码 593-612出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2016.34
关键词
Numb; Mon1; early endosome; homotypic fusion
类别
资金
- Ministry of Science & Technology, China [2014CB964602, 2012CB966802, 2011CB965100, 2010CB945600, 2009CB941402, 2007CB947202, 2013ZX09509104, 2009R0002]
- National Natural Science Foundation of China [31301125, 31071283, 30771102, 81502537, 81370457, 81271498]
- China Postdoctoral Science Foundation [2015M572383]
- Shenzhen Peacock Plan [KQCX20130628112914292]
- Shenzhen Science and Technology Program [JCYJ20150401145529014, JCYJ20150630114942300]
- Shenzhen Key Laboratory for Molecular Biology of Neural Development [ZDSY20120617112838879]
- SIAT Innovation Program for Excellent Young Researchers [201404, 201413]
- Shenzhen Institutes of Advanced Technology-CAS
- Tongji University Shanghai East Hospital
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据