Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth
Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth
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DOI：
10.1016/j.devcel.2005.09.018
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发表时间：
2005-11-01
影响因子：
11.8
通讯作者：
Hariharan, IK
中科院分区：
文献类型：
--
作者：
Moberg, KH;Schelble, S;Hariharan, IK
后生动物发育过程中生物体生长的可重复模式是遗传控制信号通路的产物。这些通路的模式化激活塑造了发育中的器官，并决定了整个生物体的形状和大小。在这里，我们表明，果蝇Tsg 101直系同源物突变的组织补丁，爆发，导致相邻的野生型组织显着过度增殖。Tsg 101蛋白在内体分选中起作用，并且需要将晚期内体并入多泡体中。Tsg 101功能受损的果蝇细胞显示Notch受体在由内体蛋白Hrs标记的细胞内隔室中积累。这导致Notch介导的信号传导和Notch靶基因未配对（upd）的异位表达增加，所述Notch靶基因未配对（upd）编码JAK-STAT途径的分泌配体。周围野生型细胞中JAK-STAT信号传导的激活与其过度生长相关。这些发现定义了一个途径，通过该途径内吞运输的变化可以以非细胞自主的方式调节组织生长。
The reproducible pattern of organismal growth during metazoan development is the product of genetically controlled signaling pathways. Patterned activation of these pathways shapes developing organs and dictates overall organismal shape and size. Here, we show that patches of tissue that are mutant for the Drosophila Tsg101 ortholog, erupted, cause dramatic overproliferation of adjacent wild-type tissue. Tsg101 proteins function in endosomal sorting and are required to incorporate late endosomes into multivesicular bodies. Drosophila cells with impaired Tsg101 function show accumulation of the Notch receptor in intracellular compartments marked by the endosomal protein Hrs. This causes increased Notch-mediated signaling and ectopic expression of the Notch target gene unpaired (upd), which encodes the secreted ligand of the JAK-STAT pathway. Activation of JAK-STAT signaling in surrounding wild-type cells correlates with their overgrowth. These findings define a pathway by which changes in endocytic trafficking can regulate tissue growth in a non-cell-autonomous manner.