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一种分泌因子 NimrodB4 促进了果蝇中吞噬细胞对凋亡细胞的清除。

A secreted factor NimrodB4 promotes the elimination of apoptotic corpses by phagocytes in Drosophila.

机构信息

Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel.

出版信息

EMBO Rep. 2021 Sep 6;22(9):e52262. doi: 10.15252/embr.202052262. Epub 2021 Aug 9.

Abstract

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.

摘要

程序性细胞死亡在发育和组织稳态中发挥着基本作用。专业和非专业的吞噬细胞能够实现对凋亡细胞的适当识别、摄取和降解,这个过程称为吞噬作用。吞噬作用的失败会导致自身免疫和神经退行性疾病。在果蝇中,Nimrod 家族的两个跨膜蛋白,Draper 和 SIMU,介导凋亡细胞尸体的识别和内化。除此之外,人们对凋亡细胞降解的调控机制知之甚少。在这里,我们研究了 Nimrod 家族的一种分泌成员 NimB4 的功能,并揭示了它在清除凋亡细胞中的关键作用。我们发现 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 突变体在胚胎发生和幼虫大脑中积累凋亡细胞尸体。我们的研究表明 NimB4 在吞噬体成熟中发挥作用,更具体地说,在吞噬体与溶酶体之间的融合中发挥作用。我们提出,类似于桥连分子,NimB4 与凋亡细胞尸体结合,启动专门用于吞噬作用的吞噬体成熟程序。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddf/8419693/42c4c7273b93/EMBR-22-e52262-g012.jpg

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