Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by delta
Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by delta
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DOI：
10.1016/s1534-5807(02)00409-4
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发表时间：
2003-01-01
影响因子：
11.8
通讯作者：
Chitnis, AB
中科院分区：
文献类型：
--
作者：
Itoh, M;Kim, CH;Chitnis, AB
由Notch信号传导介导的侧抑制导致选择被允许成为由原神经基因表达限定的结构域内的神经元的细胞。斑马鱼mib突变体胚胎中侧抑制的减少使得太多的神经祖细胞分化为神经元。mib的定位克隆揭示了它是Notch途径中编码RING泛素连接酶的基因。Mib与Delta的胞内结构域相互作用以促进其泛素化和内化。细胞移植研究表明，mib功能在信号细胞中对于有效激活邻近细胞中的Notch是必不可少的。这些观察结果支持了Notch激活的模型，其中Delta-Notch相互作用之后是Delta的内吞作用和信号传导细胞对Notch胞外结构域的转内吞作用。这促进了剩余Notch受体的膜内切割、Notch细胞内片段的释放以及邻近细胞中靶基因的激活。
Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneural gene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. These observations support a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell. This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells.