Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells.

Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells.
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DOI:
10.1126/science.1199643
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发表时间:
2011-06-03
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Banerjee U
Banerjee U
中科院分区:
其他
文献类型:
--
作者:
Mukherjee T;Kim WS;Mandal L;Banerjee U

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果蝇体内一种称为晶体细胞的血细胞在凝血和伤口愈合中起作用,需要Notch进行规范和维护。我们报道,即使在正常的氧气供应条件下,晶体细胞也会表达与哺乳动物缺氧诱导因子-α(Hif-α)同源的SIMA蛋白水平升高。在这些类血小板晶体细胞中,SIMA通过一种非规范的、配体无关的机制激活全长Notch受体信号,在正常造血发育和低氧应激期间促进血细胞存活。这种相互作用始于早期的内体,不依赖于Hif-β(果蝇中的探戈),也不激活缺氧反应靶点。对脊椎动物髓系细胞的研究表明,在氧气充足的环境中,Hif-α蛋白也有类似的上调。本研究为Hif-α/Notch相互作用提供了一种可能在哺乳动物中保守的机制范式。
A blood cell type termed crystal cell in Drosophila functions in clotting and wound healing and requires Notch for specification and maintenance. We report that crystal cells express elevated levels of Sima protein orthologous to mammalian hypoxia-inducible factor–α (Hif-α) even under conditions of normal oxygen availability. In these platelet-like crystal cells, Sima activates full-length Notch receptor signaling via a noncanonical, ligand-independent mechanism that promotes hemocyte survival during both normal hematopoietic development and hypoxic stress. This interaction initiates in early endosomes, is independent of Hif-β (Tango in Drosophila), and does not activate hypoxia response targets. Studies in vertebrate myeloid cells have shown a similar up-regulation of Hif-α protein in well-oxygenated environments. This study provides a mechanistic paradigm for Hif-α/Notch interaction that may be conserved in mammals.
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