Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4
文献类型：期刊论文
| 作者 | Huashun Li; Yuzhen Zhang; Xianming Liu; Juntao Chen; Haiyan Sun; Ke Liu; Ming Zhao; Zhihao Ding; Ximing Shao; Hongchang Li |
| 刊名 | Journal of Biological Chemistry
 |
| 出版日期 | 2017 |
| 文献子类 | 期刊论文 |
| 英文摘要 | The biological antagonism between the signaling proteins Numb and Notch has been implicated in the regulation of many developmental processes, especially in asymmetric cell division. Mechanistic studies show that Numb inactivates Notch via endocytosis and proteasomal degradation that directly reduce Notch protein levels at the cell surface. However, some aspects of how Numb antagonizes Notch remain unclear. Here, we report a novel mechanism in which Numb acts as a Notch antagonist by controlling the intracellular destination and stability of the Notch ligand Delta-like 4 (Dll4) through a postendocyticsorting process. We observed that Numb/Numblike knockdown increases the stability and cell-surface accumulation of Dll4. Further study indicated that Numb acts as a sorting switch to control the postendocytic trafficking of Dll4. Of note, the Numb/Numblike knockdown decreased Dll4 delivery to the lysosome, while increasing the recycling of Dll4 to the plasma membrane. Moreover, we demonstrate that this enrichment of Dll4 at the cell surface within Numb/Numblike knockdown cells could activate Notch signaling in neighboring cells. We also provide evidence that Numb negatively controls the Dll4 plasma membrane recycling through a well-documented recycling regulator protein AP1. In conclusion, our study has uncovered a molecular mechanism whereby Numb regulates the endocytic trafficking of the Notch ligand Dll4. Our findings provide a new perspective on how Numb counteracts Notch signaling and sheds additional critical insights into the antagonistic relationship between Numb and Notch signaling. |
| URL标识 | 查看原文 |
| 语种 | 英语 |
| WOS记录号 | WOS:000418267000023 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/12270]  |
| 专题 | 深圳先进技术研究院_医药所 |
| 作者单位 | Journal of Biological Chemistry |
| 推荐引用方式 GB/T 7714 | Huashun Li,Yuzhen Zhang,Xianming Liu,et al. Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4[J]. Journal of Biological Chemistry,2017. |
| APA | Huashun Li.,Yuzhen Zhang.,Xianming Liu.,Juntao Chen.,Haiyan Sun.,...&Yang Hong.(2017).Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4.Journal of Biological Chemistry. |
| MLA | Huashun Li,et al."Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4".Journal of Biological Chemistry (2017). |
入库方式： OAI收割
来源：深圳先进技术研究院
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