The first deltex null mutant indicates tissue-specific deltex-dependent Notch signaling in Drosophila
The first deltex null mutant indicates tissue-specific deltex-dependent Notch signaling in Drosophila
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DOI：
10.1007/s00438-005-0087-3
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发表时间：
2006-03-01
影响因子：
3.1
通讯作者：
Matsuno, K
中科院分区：
文献类型：
--
作者：
Fuwa, TJ;Hori, K;Matsuno, K
Noch(N)是一种单程跨膜受体。N信号通路是一种进化上保守的机制，它控制着各种细胞特定的过程。果蝇Deltex(Dx)是一种环状结构域E3泛素连接酶，它与N胞内结构域结合，促进N向晚期内吞体内转运，并被认为激活无毛[SU(H)]非依赖性N信号的抑制因子。然而，评估DX的重要性一直是困难的，因为在任何生物体中都没有DX家族基因的零突变。在这里，我们报道了果蝇DX的第一个零突变等位基因。我们发现DX只参与N信号的子集，但在任何发育背景下都不是必需的。DX与SU(H)之间存在较强的遗传互作，提示DX可能参与SU(H)依赖的N信号传导。我们的上位性分析表明，DX在配体下游和活化的SU(H)的上游起作用。我们还发现了一种新的DX活性，它抑制了N下游的N信号。
Notch (N) is a single-pass transmembrane receptor. The N signaling pathway is an evolutionarily conserved mechanism that controls various cell-specification processes. Drosophila Deltex (Dx), a RING-domain E3 ubiquitin ligase, binds to the N intracellular domain, promotes N's endocytic trafficking to late endosomes, and was proposed to activate Suppressor of Hairless [Su(H)]-independent N signaling. However, it has been difficult to evaluate the importance of dx, because no null mutant of a dx family gene has been available in any organism. Here, we report the first null mutant allele of Drosophila dx. We found that dx was involved only in the subsets of N signaling, but was not essential for it in any developmental context. A strong genetic interaction between dx and Su(H) suggested that dx might function in Su(H)-dependent N signaling. Our epistatic analyses suggested that dx functions downstream of the ligands and upstream of activated Su(H). We also uncovered a novel dx activity that suppressed N signaling downstream of N.