Six-microns-under acts upstream of draper in the glial phagocytosis of apoptotic neurons
Six-microns-under acts upstream of draper in the glial phagocytosis of apoptotic neurons
复制标题
DOI：
10.1016/j.cell.2008.02.052
复制
发表时间：
2008-05-02
期刊：
影响因子：
64.5
通讯作者：
Gaul, Ulrike
中科院分区：
文献类型：
--
作者：
Kurant, Estee;Axelrod, Sofia;Gaul, Ulrike
吞噬细胞邻居清除凋亡细胞对于后生动物的发育是必不可少的，但仍缺乏特征性。在这里，我们发现了一种果蝇吞噬细胞受体，六微米以下(SIMU)，它在发育过程中表达在高度吞噬细胞类型中，是神经系统中的胶质细胞和其他地方的巨噬细胞有效清除凋亡细胞所必需的。SIMU是包括CED-1和Draper(DRPR)在内的保守蛋白质家族的一部分。表型分析表明，SIMU以相同的途径作用于drpr的上游，并影响对凋亡细胞的识别和吞噬，而drpr则影响其随后的降解。SIMU可能通过其类似Emily的结构域与凋亡细胞强烈结合，但不需要膜锚定，这表明它可以作为桥梁分子发挥作用。我们的研究介绍了一个重要的因素，在组织驻留的凋亡清除，并强调了神经胶质细胞作为“半专业”吞噬细胞在神经系统中的突出作用。
The removal of apoptotic cells by phagocytic neighbors is essential for metazoan development but remains poorly characterized. Here we report the discovery of a Drosophila phagocytosis receptor, Six-microns-under (SIMU), which is expressed in highly phagocytic cell types during development and required for efficient apoptotic cell clearance by glia in the nervous system and by macrophages elsewhere. SIMU is part of a conserved family of proteins that includes CED-1 and Draper (DRPR). Phenotypic analysis reveals that simu acts upstream of drpr in the same pathway and affects the recognition and engulfment of apoptotic cells, while drpr affects their subsequent degradation. SIMU strongly binds to apoptotic cells, presumably through its EMILIN-like domain, but requires no membrane anchoring, suggesting that it can function as a bridging molecule. Our study introduces an important factor in tissue-resident apoptotic clearance and underscores the prominent role of glia as "semiprofessional'' phagocytes in the nervous system.