A secreted factor NimrodB4 promotes the elimination of apoptotic corpses by phagocytes in Drosophila.
A secreted factor NimrodB4 promotes the elimination of apoptotic corpses by phagocytes in Drosophila.
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DOI：
10.15252/embr.202052262
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发表时间：
2021-09-06
期刊：
影响因子：
7.7
通讯作者：
Lemaitre B
中科院分区：
文献类型：
--
作者：
Petrignani B;Rommelaere S;Hakim-Mishnaevski K;Masson F;Ramond E;Hilu-Dadia R;Poidevin M;Kondo S;Kurant E;Lemaitre B
程序性细胞死亡在发育和组织稳态中起着重要作用。专业和非专业吞噬细胞实现凋亡细胞的适当识别，摄取和降解，这一过程称为吞噬作用。红细胞增多症的失败导致自身免疫性和神经退行性疾病。在果蝇中，尼姆罗德家族的两种跨膜蛋白德雷珀和SIMU介导凋亡尸体的识别和内化。除了这一早期步骤之外，关于凋亡细胞降解是如何调节的知之甚少。在这里，我们研究了尼姆罗德家族的分泌成员NimB 4的功能，并揭示了其在清除凋亡细胞中的关键作用。我们发现，NimB4表达的巨噬细胞和神经胶质细胞，在果蝇的两种主要类型的吞噬细胞。类似于德雷珀突变体，NimB4突变体在胚胎发生期间和幼虫脑中积累凋亡尸体。我们的研究指出了NimB4在吞噬体成熟中的作用，更具体地说，在吞噬体和溶酶体之间的融合中。我们提出，类似于桥接分子，NimB4结合到凋亡的尸体，从事吞噬体成熟程序致力于吞噬作用。这项研究表明分泌蛋白NimB4在吞噬体成熟中的作用。类似于桥接分子，NimB4结合到凋亡尸体上，以参与专门用于吞噬作用的吞噬体成熟程序。
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. This study suggests a role of the secreted protein NimB4 in phagosome maturation. Similar to bridging molecules, NimB4 binds to apoptotic corpses to engage a phagosome maturation program dedicated to efferocytosis.
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影响因子：
64.5
作者：
Davie K;Janssens J;Koldere D;De Waegeneer M;Pech U;Kreft Ł;Aibar S;Makhzami S;Christiaens V;Bravo González-Blas C;Poovathingal S;Hulselmans G;Spanier KI;Moerman T;Vanspauwen B;Geurs S;Voet T;Lammertyn J;Thienpont B;Liu S;Konstantinides N;Fiers M;Verstreken P;Aerts S
通讯作者：
Aerts S
影响因子：
8.8
作者：
Hakim-Mishnaevski, Ketty;Flint-Brodsly, Naama;Kurant, Estee
通讯作者：
Kurant, Estee
影响因子：
10.5
作者：
Chen, P;Nordstrom, W;Abrams, JM
通讯作者：
Abrams, JM
DOI：
10.1083/jcb.201008119
发表时间：
2011-02-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Akbar MA;Tracy C;Kahr WH;Krämer H
通讯作者：
Krämer H
DOI：
10.1083/jcb.201004096
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Elliott MR;Ravichandran KS
通讯作者：
Ravichandran KS