在EGF repeat-8中发生的一种突变使得Serrate/Jagged和Delta家族连体之间存在差异
Shinya Yamamoto1, Wu-Lin Charng, Nadia A Rana
1Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Science (New York, N.Y.)
|December 1, 2012
概括
在Notch受体中的突变.
科学领域:
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 分子遗传学 分子遗传学
背景情况:
- 痕信号对于发育至关重要,并与癌症和中风等疾病有关.
- 诺奇受体与配体Delta和Serrate相互作用,但这种选择性的分子基础尚不清楚.
研究的目的:
- 确定负责连接体选择性的Notch受体的特定域.
- 为了了解底层的分子机制,诺奇-连接体的歧视.
主要方法:
- 利用Drosophila的遗传选来隔离影响Notch信号的突变.
- 标志着诺奇突变,这是表皮生长因子重复-8 (EGFr-8) 的误解突变.
- 研究了突变的诺奇受体与其连接体的结合亲缘关系,并检查了哺乳动物诺奇2的同源突变.
主要成果:
- 鉴定了Notch (拼图) 突变,该突变会损害Serrate依赖信号传输,但不会损害Delta依赖信号传输.
- 诺奇突变导致缺陷的Serrate结合,这是由于EGFr-8中的误解突变导致的.
- 哺乳动物Notch2的一种同源突变也显示了Jagged1信号的缺陷,表明进化保护.
结论:
- 在EGFr-8中,一个在进化过程中保存的氨酸残留物对于Notch受体的连接体选择性至关重要.
- 这一发现为理解Notch-ligand相互作用和Notch-dependent信号通路提供了分子基础.
- 鉴定的突变是研究各种依赖的细胞过程和疾病的宝贵工具.
相关概念视频
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Cell Sorting During Development
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02:33Hedgehog Signaling Pathway
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01:16TGF - β Signaling Pathway
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