Identification of calreticulin as a marker for phagocytosis of apoptotic cells in Drosophila
Identification of calreticulin as a marker for phagocytosis of apoptotic cells in Drosophila
复制标题
DOI：
10.1016/j.yexcr.2006.10.027
复制
发表时间：
2007-02-01
影响因子：
3.7
通讯作者：
Nakanishi, Yoshinobu
中科院分区：
文献类型：
--
作者：
Kuraishi, Takayuki;Manaka, Junko;Nakanishi, Yoshinobu
凋亡细胞的吞噬作用是通过靶细胞表面的吞噬标志物与吞噬细胞受体之间的特异性相互作用而启动的。虽然许多分子已被提出作为哺乳动物的吞噬标记物和受体，但关于这些分子的身份的信息对于无脊椎动物是有限的。钙网蛋白是一种在内质网腔中起作用的分子伴侣，最近被报道是第二个被吞噬细胞识别的哺乳动物凋亡细胞的通用标志物，膜磷脂磷脂酰丝氨酸是第一个。我们在这里询问钙网蛋白是否作为果蝇吞噬作用的标志物。果蝇血细胞衍生的1（2）mbn细胞，我们以前发现发生独立的磷脂酰丝氨酸的凋亡S2细胞的吞噬作用，被抑制通过添加抗钙网蛋白抗体。当靶细胞而不是吞噬细胞与抗体预孵育时观察到这种抑制。此外，RNA干扰介导的钙网蛋白表达在凋亡S2细胞中的减少，而不是在1（2）mbn细胞中，降低了吞噬作用的水平。免疫细胞化学分析表明，钙网蛋白广泛分布在S2细胞的表面。诱导凋亡后，细胞表面钙网蛋白似乎形成聚集体，其数量没有变化。此外，在胚胎中的突变果蝇株，表达钙网蛋白在一个降低的水平，凋亡细胞的吞噬作用的水平是约一半的野生型菌株的胚胎中观察到的。这些结果共同表明，钙网蛋白是第一个被确定为果蝇吞噬细胞吞噬凋亡细胞的标志物的分子。(c)2006年爱思唯尔公司All rights reserved.
Apoptotic cell phagocytosis is initiated through the specific interaction between markers for phagocytosis present at the surface of targets and their receptors of phagocytes. Although many molecules have been proposed to be phagocytosis markers and receptors in mammals, information as to the identity of those molecules is limited for invertebrate animals. Calreticulin, a molecular chaperone that functions in the lumen of the endoplasmic reticulum, was recently reported to be the second general marker, the membrane phospholipid phosphatidylserine being the first, for mammalian apoptotic cells to be recognized by phagocytes. We here asked whether or not calreticulin serves as a marker for phagocytosis in Drosophila. Phagocytosis of apoptotic S2 cells by Drosophila hemocyte-derived 1(2)mbn cells, which we previously showed to occur independent of phosphatidylserine, was inhibited by the addition of anti-calreticulin antibody. This inhibition was observed when the target cells, but not phagocytes, were pre-incubated with the antibody. In addition, RNA interference-mediated reduction of calreticulin expression in apoptotic S2 cells, but not in 1(2)mbn cells, reduced the level of phagocytosis. An immunocytochemical analysis revealed that calreticulin is widely distributed at the surface of viable S2 cells. After the induction of apoptosis, cell surface calreticulin seemed to form aggregates, with no change in its amount. Furthermore, in embryos of a mutant Drosophila strain that expresses calreticulin at a reduced level, the level of phagocytosis of apoptotic cells was about a half of that observed in embryos of a wild-type strain. These results collectively indicate that calreticulin is the first molecule to be identified as a marker for phagocytosis of apoptotic cells by Drosophila phagocytes. (c) 2006 Elsevier Inc. All rights reserved.