Notch signaling modulates the nuclear localization of carboxy-terminal-phosphorylated smad2 and controls the competence of ectodermal cells for activin A
Notch signaling modulates the nuclear localization of carboxy-terminal-phosphorylated smad2 and controls the competence of ectodermal cells for activin A
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DOI：
10.1016/j.mod.2004.12.006
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发表时间：
2005-05-01
影响因子：
2.6
通讯作者：
Asashima, M
中科院分区：
文献类型：
--
作者：
Abe, T;Furue, M;Asashima, M
中胚层功能丧失(LMC)是一种众所周知但鲜为人知的现象，即预期的外胚层细胞(动物帽)在原肠形成开始后失去诱导信号的能力，如激活素A，以诱导中胚层基因和组织。Noch信号可以延迟激活素A在动物帽中的LMC开始[Coffman，C.R.，Skoglund，P.，Harris，W.A.，Kintner，C.R.，1993。Xotch胞外缺失基因的表达改变了非洲爪哇胚胎的细胞命运。单元73,659-671]，尽管发生这种调制的机制仍然未知。在这里，我们表明Notch信号也延迟了整个胚胎中LMC的开始，就像它在动物帽中所做的那样。为了更好地理解这种作用和LMC本身的机制，我们研究了Notch信号在激活素信号转导通路的哪一步作用于LMC的时间。在我们的系统中，在对照和Notch激活的动物CAP中，ALK4(激活素I型受体)在激活素A刺激后保持对Smad2 C末端区域的磷酸化能力。然而，只有在Notch激活的动物帽子中，C末端磷酸化的Smad2才能与Smad4结合并聚集在细胞核中。我们的结论是，LMC的诱导是因为C末端磷酸化的Smad2失去了与Smad4结合的能力，因此不能在细胞核内积聚。Notch信号激活恢复了C末端磷酸化的Smad2与Smad4结合的能力，导致LMC发病延迟。(C)2005爱思唯尔爱尔兰有限公司。保留所有权利。
Loss of mesodermal competence (LMC) during Xenopus development is a well known but little understood phenomenon that prospective ectodermal cells (animal caps) lose their competence for inductive signals, such as activin A, to induce mesodermal genes and tissues after the start of gastrulation. Notch signaling can delay the onset of LMC for activin A in animal caps [Coffman, C.R., Skoglund, P., Harris, W.A., Kintner, C.R., 1993. Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos. Cell 73, 659-671], although the mechanism by which this modulation occurs remains unknown. Here, we show that Notch signaling also delays the onset of LMC in whole embryos, as it did in animal caps. To better understand this effect and the mechanism of LMC itself, we investigated at which step of activin signal transduction pathway the Notch signaling act to affect the timing of the LMC. In our system, ALK4 (activin type I receptor) maintained the ability to phosphorylate the C-terminal region of smad2 upon activin A stimulus after the onset of LMC in both control- and Notch-activated animal caps. However, C-terminal-phosphorylated smad2 could bind to smad4 and accumulate in the nucleus only in Notch-activated animal caps. We conclude that LMC was induced because C-terminal-phosphorylated smad2 lost its ability to bind to smad4, and consequently could not accumulate in the nucleus. Notch signal activation restored the ability of C-terminal-phosphorylated smad2 to bind to smad4, resulting in a delay in the onset of LMC. (c) 2005 Elsevier Ireland Ltd. All rights reserved.