bfc, a novel serpent co-factor for the expression of croquemort, regulates efferocytosis in Drosophila melanogaster.
bfc, a novel serpent co-factor for the expression of croquemort, regulates efferocytosis in Drosophila melanogaster.
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bfc 是表达 croquemort 的新型蛇辅因子，可调节果蝇的胞吞作用
DOI：
10.1371/journal.pgen.1009947
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发表时间：
2021-12
期刊：
影响因子：
4.5
通讯作者：
Xiao H
中科院分区：
文献类型：
--
作者：
Zheng Q;Gao N;Sun Q;Li X;Wang Y;Xiao H
胞饮作用是吞噬细胞在发育过程中识别、吞噬和消化（或清除）凋亡细胞的过程。受损的红细胞增多症与发育缺陷和自身免疫性疾病有关。在黑腹果蝇中，凋亡细胞的识别需要吞噬细胞表面受体，包括清道夫受体CD36相关蛋白Croquemort（Crq，由crq编码）。事实上，Crq表达在凋亡细胞的存在下以及响应于过度凋亡而上调。在这里，我们发现了一个新的基因bfc（croquemort的助推器），它在红细胞增多症中起作用，特别是crq表达的调节。我们发现Bfc蛋白与加塔转录因子Serpent（Srp）的锌指结构域相互作用，以增强其与crq启动子的直接结合，因此，它们一起调节crq表达和胞浆细胞增多。总的来说，我们发现Bfc作为Srp辅助因子上调crq编码受体的转录，从而促进巨噬细胞凋亡。因此，本研究阐明了吞噬细胞如何整合凋亡细胞信号介导吞噬作用。通过巨噬细胞（白色血细胞的一种亚型）等专门细胞迅速清除凋亡细胞，是从蠕虫到人类的所有多细胞生物发育过程中塑造组织的关键事件。死亡细胞的去除缺陷，一个被称为凋亡细胞（AC）清除的过程，可能导致自身免疫性疾病，如系统性红斑狼疮（SLE）和神经退行性疾病，如阿尔茨海默病的发展。Croquemort（Crq）是一种果蝇CD 36相关受体，是巨噬细胞识别和吞噬AC所必需的。本研究通过转录组学分析和RNAi筛选，在果蝇类巨噬细胞S2细胞中发现了12个清除AC所需的基因。特别是，我们发现了一个新的基因，bfc（croquemort的助推器），通过crq转录表达的特异性调节参与凋亡细胞的清除。我们证明，加塔转录因子Serpent（Srp）直接结合到crq启动子，而Bfc通过其与Srp锌指结构域的相互作用加强这种结合。因此，我们提出了一个模型，其中Bfc与Srp合作，以提高crq的表达，并随后诱导凋亡的细胞清除在果蝇。
Efferocytosis is the process by which phagocytes recognize, engulf, and digest (or clear) apoptotic cells during development. Impaired efferocytosis is associated with developmental defects and autoimmune diseases. In Drosophila melanogaster, recognition of apoptotic cells requires phagocyte surface receptors, including the scavenger receptor CD36-related protein, Croquemort (Crq, encoded by crq). In fact, Crq expression is upregulated in the presence of apoptotic cells, as well as in response to excessive apoptosis. Here, we identified a novel gene bfc (booster for croquemort), which plays a role in efferocytosis, specifically the regulation of the crq expression. We found that Bfc protein interacts with the zinc finger domain of the GATA transcription factor Serpent (Srp), to enhance its direct binding to the crq promoter; thus, they function together in regulating crq expression and efferocytosis. Overall, we show that Bfc serves as a Srp co-factor to upregulate the transcription of the crq encoded receptor, and consequently boosts macrophage efferocytosis in response to excessive apoptosis. Therefore, this study clarifies how phagocytes integrate apoptotic cell signals to mediate efferocytosis. The swift removal of apoptotic cells by specialized cells such as macrophages (a subtype of white blood cells), is a critical event in shaping tissues during the development of all multicellular organisms, from worms to humans. Defects in the removal of dying cells, a process known as the clearance of apoptotic cells (ACs), can contribute to the development of autoimmune disorders such as systemic Lupus erythematosus (SLE) and neurodegenerative diseases like Alzheimer’s disease. Croquemort (Crq), a Drosophila CD36-related receptor, is required for the recognition and engulfment of ACs in macrophages. In this study, via transcriptomic analysis and RNAi screening, we discovered 12 genes required for the clearance of ACs in macrophage-like S2 cells in Drosophila. In particular, we identified a novel gene, bfc (booster for croquemort), involved in apoptotic cell clearance via the specific regulation of the crq transcriptional expression. We demonstrate that the GATA transcription factor Serpent (Srp) directly binds to the crq promoter, while Bfc strengthens this binding via its interaction with the Srp zinc finger domain. Therefore, we propose a model in which Bfc cooperates with Srp to enhance the expression of crq and subsequently induce apoptotic cell clearance in Drosophila melanogaster.
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影响因子：
4.3
作者：
Meehan TL;Kleinsorge SE;Timmons AK;Taylor JD;McCall K
通讯作者：
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作者：
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影响因子：
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作者：
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影响因子：
14.9
作者：
Han, KH
通讯作者：
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