Roles of Drosophila Deltex in Notch receptor endocytic trafficking and activation
Roles of Drosophila Deltex in Notch receptor endocytic trafficking and activation
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DOI：
10.1111/j.1365-2443.2011.01488.x
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发表时间：
2011-03
期刊：
影响因子：
2.1
通讯作者：
Kenta Yamada;Takashi J. Fuwa;T. Ayukawa;Tsubasa Tanaka;A. Nakamura;M. Wilkin;M. Baron;K. Matsuno
中科院分区：
文献类型：
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作者：
Kenta Yamada;Takashi J. Fuwa;T. Ayukawa;Tsubasa Tanaka;A. Nakamura;M. Wilkin;M. Baron;K. Matsuno
由Notch受体（N）介导的细胞信号传导调节许多细胞命运决定，并且部分由N的内吞运输控制。果蝇deltex（dx）编码一种进化上保守的N信号调节因子，一种E3-泛素连接酶，它泛素化N的细胞内结构域。尽管在dx过表达的研究中显示Dx在N内吞作用中起作用，但内源性Dx的作用仍然隐藏。在这里，我们研究了dx缺失果蝇突变体中的N内吞作用，发现N运输至少需要两个步骤：N从质膜掺入内吞囊泡以及N从早期核内体转运到溶酶体。在没有Dx功能的情况下，N在未知的内吞隔室中稳定，在那里它可能与运输到溶酶体绝缘。我们还发现，典型的N信号和Dx介导的N信号在两个不同的内吞隔室中被激活，分别在N被掺入多泡体（MVB）腔间囊泡之前和N从MVB转运之后。Dx介导的N信号被激活的内吞区室似乎与N运输中内源性Dx的活性一致。这些发现扩展了我们对N的运输和激活是如何相互关联的理解。
Cell signaling mediated by the Notch receptor (N) regulates many cell‐fate decisions and is partly controlled by the endocytic trafficking of N. Drosophila deltex (dx) encodes an evolutionarily conserved regulator of N signaling, an E3‐ubiquitin ligase, which ubiquitinates N’s intracellular domain. Although Dx was shown to function in N endocytosis in studies of dx over‐expression, the roles of endogenous Dx have remained hidden. Here, we investigated N endocytosis in a dx‐null Drosophila mutant and found that endogenous Dx is required for at least two steps of N trafficking: the incorporation of N into endocytic vesicles from the plasma membrane and the transport of N from early endosomes to lysosomes. In the absence of Dx functions, N was stabilized in unknown endocytic compartments, where it was probably insulated from transport to lysosomes. We also found that canonical N signaling and Dx‐mediated N signaling are activated in two different endocytic compartments, before N is incorporated into multivesicular body (MVB) interluminal vesicles and after N is transported from MVBs, respectively. The endocytic compartment in which Dx‐mediated N signaling is activated appears to coincide with the activity of endogenous Dx in N trafficking. These findings extend our understanding of how N’s trafficking and activation are correlated.