Drosophila deltex mediates suppressor of hairless-independent and late-endosomal activation of Notch signaling
Drosophila deltex mediates suppressor of hairless-independent and late-endosomal activation of Notch signaling
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DOI：
10.1242/dev.01448
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发表时间：
2004-11-01
期刊：
影响因子：
4.6
通讯作者：
Matsuno, K
中科院分区：
文献类型：
--
作者：
Hori, K;Fostier, M;Matsuno, K
Notch（N）信号是一种进化上保守的机制，调节许多细胞命运决定。deltex（dx）编码E3-泛素连接酶，其结合N的胞内结构域并正调节N信号传导。然而，Dx作用的确切机制尚不清楚。在这里，我们发现Dx是必需的，足以激活经典的Su（H）依赖性N信号通路的基因靶点的表达。尽管Dx需要N和与Su（H）结合位点重叠的顺式作用元件，但Dx以不依赖于Delta（DI）/Serrate（Ser）配体或Su（H）的方式激活N信号传导的靶增强子，即残基的背腹侧隔室边界增强子（vgBE）。Dx导致N从顶端细胞表面移动到晚期内体，在那里它稳定地积累并与Dx共定位。与此相一致的是，dx基因的存在下，N的内吞囊泡所需的。最后，通过显性负性形式的Rab 5阻断N从质膜到晚期内体的转运抑制了Dx介导的N信号转导的激活，表明N在晚期内体中的积累是Dx介导的Su（H）非依赖性N信号转导所必需的。
Notch (N) signaling is an evolutionarily conserved mechanism that regulates many cell-fate decisions. deltex (dx) encodes an E3-ubiquitin ligase that binds to the intracellular domain of N and positively regulates N signaling. However, the precise mechanism of Dx action is unknown. Here, we found that Dx was required and sufficient to activate the expression of gene targets of the canonical Su(H)-dependent N signaling pathway. Although Dx required N and a cis-acting element that overlaps with the Su(H)-binding site, Dx activated a target enhancer of N signaling, the dorsoventral compartment boundary enhancer of vestigial (vgBE), in a manner that was independent of the Delta (DI)/Serrate (Ser) ligands- or Su(H). Dx caused N to be moved from the apical cell surface into the late-endosome, where it accumulated stably and co-localized with Dx. Consistent with this, the dx gene was required for the presence of N in the endocytic vesicles. Finally, blocking the N transportation from the plasma membrane to the late-endosome by a dominant-negative form of Rab5 inhibited the Dx-mediated activation of N signaling, suggesting that the accumulation of N in the late-endosome was required for the Dx-mediated Su(H)independent N signaling.