Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells
Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells
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DOI：
10.1038/emboj.2009.343
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发表时间：
2009-12-16
期刊：
影响因子：
11.4
通讯作者：
Nakanishi, Yoshinobu
中科院分区：
文献类型：
--
作者：
Kuraishi, Takayuki;Nakagawa, Yukiko;Nakanishi, Yoshinobu
吞噬细胞清除正在凋亡的细胞对于动物发育和组织稳态是必要的。 Draper 是秀丽隐杆线虫吞噬受体 CED-1 的同源物，负责果蝇中凋亡细胞的吞噬作用，但其配体可能存在于凋亡细胞上仍然未知。分离出与 Draper 细胞外区域结合的内质网蛋白。这种蛋白质（我们将其命名为 Pretaporter）的缺失导致胚胎中凋亡细胞清除水平降低，而突变果蝇中预转运蛋白的过度表达则挽救了这一缺陷。遗传分析结果表明 Pretaporter 与 Draper 和相应的信号介质存在功能性相互作用。诱导细胞凋亡后，Pretaporter 暴露在细胞表面，在表面人工表达 Pretaporter 的细胞变得对 Draper 介导的吞噬作用敏感。最后，与 Pretaporter 一起孵育增强了吞噬细胞中 Draper 的酪氨酸磷酸化。这些结果共同表明，在细胞凋亡过程中，Pretaporter 从内质网重新定位到细胞表面，在凋亡细胞的吞噬作用中充当 Draper 的配体。 EMBO 杂志 (2009) 28, 3868-3878。 doi：10.1038/emboj.2009.343； 2009 年 11 月 19 日在线发布
Phagocytic removal of cells undergoing apoptosis is necessary for animal development and tissue homeostasis. Draper, a homologue of the Caenorhabditis elegans phagocytosis receptor CED-1, is responsible for the phagocytosis of apoptotic cells in Drosophila, but its ligand presumably present on apoptotic cells remains unknown. An endoplasmic reticulum protein that binds to the extracellular region of Draper was isolated. Loss of this protein, which we name Pretaporter, led to a reduced level of apoptotic cell clearance in embryos, and the overexpression of pretaporter in the mutant flies rescued this defect. Results from genetic analyses suggested that Pretaporter functionally interacts with Draper and the corresponding signal mediators. Pretaporter was exposed at the cell surface after the induction of apoptosis, and cells artificially expressing Pretaporter at their surface became susceptible to Draper-mediated phagocytosis. Finally, the incubation with Pretaporter augmented the tyrosine-phosphorylation of Draper in phagocytic cells. These results collectively suggest that Pretaporter relocates from the endoplasmic reticulum to the cell surface during apoptosis to serve as a ligand for Draper in the phagocytosis of apoptotic cells. The EMBO Journal ( 2009) 28, 3868-3878. doi: 10.1038/emboj.2009.343; Published online 19 November 2009