Department of Biology, Boston University, Boston, MA 02215, USA.
Program in Biochemistry and Molecular Biology, Boston University, Boston, MA 02215, USA.
G3 (Bethesda). 2021 Feb 9;11(2). doi: 10.1093/g3journal/jkaa066.
Programmed cell death and cell corpse clearance are an essential part of organismal health and development. Cell corpses are often cleared away by professional phagocytes such as macrophages. However, in certain tissues, neighboring cells known as nonprofessional phagocytes can also carry out clearance functions. Here, we use the Drosophila melanogaster ovary to identify novel genes required for clearance by nonprofessional phagocytes. In the Drosophila ovary, germline cells can die at multiple time points. As death proceeds, the epithelial follicle cells act as phagocytes to facilitate the clearance of these cells. We performed an unbiased kinase screen to identify novel proteins and pathways involved in cell clearance during two death events. Of 224 genes examined, 18 demonstrated severe phenotypes during developmental death and clearance while 12 demonstrated severe phenotypes during starvation-induced cell death and clearance, representing a number of pathways not previously implicated in phagocytosis. Interestingly, it was found that several genes not only affected the clearance process in the phagocytes, but also non-autonomously affected the process by which germline cells died. This kinase screen has revealed new avenues for further exploration and investigation.
程序性细胞死亡和细胞尸清除是生物体健康和发育的重要组成部分。细胞尸通常被专业的吞噬细胞(如巨噬细胞)清除。然而,在某些组织中,相邻的细胞(称为非专业吞噬细胞)也可以发挥清除功能。在这里,我们使用黑腹果蝇的卵巢来鉴定非专业吞噬细胞清除所需的新基因。在果蝇的卵巢中,生殖细胞可以在多个时间点死亡。随着死亡的进行,上皮滤泡细胞充当吞噬细胞,促进这些细胞的清除。我们进行了一项无偏激酶筛选,以鉴定在两个死亡事件中参与细胞清除的新蛋白和途径。在检查的 224 个基因中,有 18 个在发育性死亡和清除过程中表现出严重表型,而 12 个在饥饿诱导的细胞死亡和清除过程中表现出严重表型,这代表了一些以前未涉及吞噬作用的途径。有趣的是,发现有几个基因不仅影响吞噬细胞的清除过程,而且还非自主地影响生殖细胞死亡的过程。这个激酶筛选揭示了进一步探索和研究的新途径。