诺奇和Hif-alpha之间的相互作用影响了多索菲拉血细胞的发育和生存
Tina Mukherjee1, William Sang Kim, Lolitika Mandal
1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
Science (New York, N.Y.)
|June 4, 2011
概括
德罗斯菲拉晶体细胞利用Sima (低氧诱导因子-α) 来非正规地激活Notch信号,提高血细胞的存活率. 这种保存机制可能适用于哺乳动物细胞,影响血液发育和应激反应.
科学领域:
- 发育生物学是发展生物学.
- 细胞信号传递 细胞信号传递
- 血液形成 血液形成 血液形成
背景情况:
- 果虫晶体细胞对于凝血和伤口愈合至关重要,需要Notch信号.
- 晶体细胞表现出高的Sima (低氧诱导因子-α) 水平,即使在正常的氧气中.
- 缺氧诱导的α因子 (Hif-α) 在诺尔莫克西亚上调在脊椎动物骨髓状细胞中被观察到.
研究的目的:
- 为了研究drosophila晶体细胞中Sima介导的Notch激活的非正规机制.
- 阐明这种相互作用在正常和缺氧条件下的血细胞存活中的作用.
- 为了探索Hif-α/Notch相互作用在哺乳动物中的潜在保护.
主要方法:
- 在Drosophila晶体细胞中分析Sima和Notch信号.
- 调查相互作用对Hif-β (Tango) 和其启动地点的依赖性.
- 将研究结果与脊椎动物髓状细胞研究进行比较.
主要成果:
- 西马激活了全长的Notch受体信号,以一种连接体独立的方式.
- 这种非正规的途径促进了在发育和缺氧压力期间的血细胞存活.
- 相互作用发生在早期的内分体中,并且独立于Hif-β (Tango).
- 低氧反应目标不会被这种Sima-Notch相互作用激活.
结论:
- 一个新的,非正规的Hif-α/Notch通路调节了Drosophila中的血细胞生存.
- 这种独立于规范性缺氧反应的机制可能在各个物种中保持不变.
- 为Hif-α和Notch相互作用提供了一个机械范式,这些相互作用可能与哺乳动物血液形成有关.
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...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...