Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
J Cell Biol. 2012 Jan 9;196(1):65-83. doi: 10.1083/jcb.201106088. Epub 2012 Jan 2.
Notch signaling governs binary cell fate determination in asymmetrically dividing cells. Through a forward genetic screen we identified the fly homologue of Eps15 homology domain containing protein-binding protein 1 (dEHBP1) as a novel regulator of Notch signaling in asymmetrically dividing cells. dEHBP1 is enriched basally and at the actin-rich interface of pII cells of the external mechanosensory organs, where Notch signaling occurs. Loss of function of dEHBP1 leads to up-regulation of Sanpodo, a regulator of Notch signaling, and aberrant trafficking of the Notch ligand, Delta. Furthermore, Sec15 and Rab11, which have been previously shown to regulate the localization of Delta, physically interact with dEHBP1. We propose that dEHBP1 functions as an adaptor molecule for the exocytosis and recycling of Delta, thereby affecting cell fate decisions in asymmetrically dividing cells.
Notch 信号通路在不对称分裂细胞中控制二元细胞命运的决定。通过正向遗传学筛选,我们发现果蝇同源物 Eps15 同源结构域包含蛋白结合蛋白 1(dEHBP1)是不对称分裂细胞中 Notch 信号通路的新型调节因子。dEHBP1 在外部机械感受器器官的 pII 细胞的基底和富含肌动蛋白的界面处富集,Notch 信号通路发生于此。dEHBP1 的功能丧失会导致 Notch 信号通路的调节因子 Sanpodo 的上调,以及 Notch 配体 Delta 的异常运输。此外,先前已显示 Sec15 和 Rab11 调节 Delta 的定位,它们与 dEHBP1 物理相互作用。我们提出,dEHBP1 作为 Delta 的胞吐作用和再循环的衔接分子发挥作用,从而影响不对称分裂细胞中的细胞命运决定。