Programmed cell death plays a fundamental role in development and tissue homeostasis. Professional and non-professional phagocytes achieve the proper recognition, uptake, and degradation of apoptotic cells, a process called efferocytosis. Failure in efferocytosis leads to autoimmune and neurodegenerative diseases. In Drosophila, two transmembrane proteins of the Nimrod family, Draper and SIMU, mediate the recognition and internalization of apoptotic corpses. Beyond this early step, little is known about how apoptotic cell degradation is regulated. Here, we study the function of a secreted member of the Nimrod family, NimB4, and reveal its crucial role in the clearance of apoptotic cells. We show that NimB4 is expressed by macrophages and glial cells, the two main types of phagocytes in Drosophila. Similar to draper mutants, NimB4 mutants accumulate apoptotic corpses during embryogenesis and in the larval brain. Our study points to the role of NimB4 in phagosome maturation, more specifically in the fusion between the phagosome and lysosomes. We propose that similar to bridging molecules, NimB4 binds to apoptotic corpses to engage a phagosome maturation program dedicated to efferocytosis.

中文翻译：

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分泌因子 NimrodB4 促进果蝇吞噬细胞清除凋亡尸体

程序性细胞死亡在发育和组织稳态中起着重要作用。专业和非专业的吞噬细胞实现对凋亡细胞的正确识别、摄取和降解，这一过程称为胞吞作用。胞吞作用失败会导致自身免疫性疾病和神经退行性疾病。在果蝇中，Nimrod 家族的两种跨膜蛋白 Draper 和 SIMU 介导凋亡尸体的识别和内化。除了这个早期步骤之外，关于如何调节凋亡细胞降解知之甚少。在这里，我们研究了 Nimrod 家族分泌成员 NimB4 的功能，并揭示其在清除凋亡细胞中的关键作用。我们表明 NimB4 由巨噬细胞和神经胶质细胞表达，这是果蝇中两种主要的吞噬细胞类型. 与draper突变体类似，NimB4突变体在胚胎发生过程中和幼虫脑中积累凋亡尸体。我们的研究指出 NimB4 在吞噬体成熟中的作用，更具体地说是在吞噬体和溶酶体之间的融合中。我们建议类似于桥接分子，NimB4 与凋亡尸体结合以参与专用于胞吞作用的吞噬体成熟程序。