Numb regulates the balance between Notch recycling and late-endosome targeting in Drosophila neural progenitor cells.
Numb regulates the balance between Notch recycling and late-endosome targeting in Drosophila neural progenitor cells.
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DOI：
10.1091/mbc.e15-11-0751
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发表时间：
2016-09-15
影响因子：
3.3
通讯作者：
Roegiers F
中科院分区：
文献类型：
--
作者：
Johnson SA;Zitserman D;Roegiers F
稳态和脉冲标记技术用于跟踪果蝇感觉器官前体细胞中的Notch受体。Numb和L（2）gl拮抗Notch受体库，并且Numb促进Notch靶向果蝇神经祖细胞中的晚期内体以调节Notch信号传导和细胞命运。Notch信号通路在动物发育和人类疾病中起着重要作用。已显示膜区室中Notch受体水平的调节在多种情况下影响信号传导。在这里，我们使用稳态和脉冲标记技术来跟踪果蝇感觉器官前体细胞中的Notch受体。我们发现，内体衔接蛋白Numb调节水平的Notch受体贩运Rab7标记的晚期内体，但不是早期内体。使用我们开发的一种检测方法，当Notch受体通过内吞系统移动时标记不同的Notch受体池，我们表明Numb特异性抑制回收的Notch受体亚群，并且Numb突变体中过量的Notch信号需要回收内体GTdR Rab11活性。因此，我们的数据表明，Numb控制Notch受体回收和受体靶向晚期内体之间的平衡，以调节果蝇神经祖细胞不对称细胞分裂后的信号输出。
Steady-state and pulse-labeling techniques are used to follow Notch receptors in sensory organ precursor cells in Drosophila. Numb and L(2)gl antagonize a pool of Notch receptors, and Numb promotes Notch targeting to late endosomes in Drosophila neural progenitors to regulate Notch signaling and cell fate. The Notch signaling pathway plays essential roles in both animal development and human disease. Regulation of Notch receptor levels in membrane compartments has been shown to affect signaling in a variety of contexts. Here we used steady-state and pulse-labeling techniques to follow Notch receptors in sensory organ precursor cells in Drosophila. We find that the endosomal adaptor protein Numb regulates levels of Notch receptor trafficking to Rab7-labeled late endosomes but not early endosomes. Using an assay we developed that labels different pools of Notch receptors as they move through the endocytic system, we show that Numb specifically suppresses a recycled Notch receptor subpopulation and that excess Notch signaling in numb mutants requires the recycling endosome GTPase Rab11 activity. Our data therefore suggest that Numb controls the balance between Notch receptor recycling and receptor targeting to late endosomes to regulate signaling output after asymmetric cell division in Drosophila neural progenitors.