Programmed cell clearance: From nematodes to humans

Klöditz, Katharina; Chen, Yu-Zen; Xue, Ding; Fadeel, Bengt

doi:10.1016/j.bbrc.2016.12.005

Cited by 19 publications

(10 citation statements)

References 79 publications

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“…Furthermore, in addition to different cell death modalities, there is also considerable heterogeneity among macrophages and other phagocytes 40 . To conclude, we suggest that cell clearance—the final stage of the cell death process—should be taken into account in the classification of different modes of cell death 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Several different forms of (programmed) cell death have been identified which can be distinguished by specific morphological features and/or corresponding biochemical processes (e.g., activation of specific kinases, proteases, and nucleases). Programmed cell clearance, in turn, is a conserved process of elimination of cell corpses 1,2 . However, it is not fully understood how phagocytes recognize and distinguish between different types of cell death.…”

Section: Introductionmentioning

confidence: 99%

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Three cell deaths and a funeral: macrophage clearance of cells undergoing distinct modes of cell death

Klöditz

Fadeel

2019

Cell Death Discovery

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117

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Macrophage clearance of apoptotic cells has been extensively investigated, but less is known regarding the clearance of cells dying by other forms of programmed cell death, e.g., necroptosis or ferroptosis. Here, we established a model of three different cell deaths using the same cell line and the occurrence of distinct cell death modalities was verified by using the specific inhibitors, zVAD-fmk, necrostatin-1, and ferrostatin-1, respectively. Cell death was characterized by using transmission electron microscopy (TEM), the gold standard for the demarcation of different cell death modalities. Moreover, using annexin V as a probe, we could detect surface exposure of phosphatidylserine (PS) in all three types of cell death, and this was confirmed by using specific anti-PS antibodies. We then co-cultured the cells with human monocyte-derived macrophages and found that cells dying by all three death modalities were engulfed by macrophages. Macrophage clearance of apoptotic cells was more efficient when compared to necroptotic and ferroptotic cells with multiple internalized target cells per macrophage, as shown by TEM. We propose that clearance of dying cells also should be taken into account in the classification of different cell death modalities.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Three cell deaths and a funeral: macrophage clearance of cells undergoing distinct modes of cell death

Klöditz

Fadeel

2019

Cell Death Discovery

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117

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“…3). Phosphatidylserine is universally present in the inner leaflet of the plasma membrane in all multicellular organisms ranging from mammals to nematodes (42). As an important component in the cell clearance pathways, PS becomes externalized during apoptosis to signal for cell clearance.…”

Section: Resultsmentioning

confidence: 99%

The crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association

Tao¹

2017

J Immunol Tech Infect Dis

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Many enveloped viruses encode a matrix protein. In the influenza A virus, the matrix protein M1 polymerizes into a rigid protein layer underneath the viral envelope to help enforce the shape and structural integrity of intact viruses. The influenza virus M1 is also known to mediate virus budding as well as the nuclear export of the viral nucleocapsids and their subsequent packaging into nascent viral particles. Despite extensive studies on the influenza A virus M1 (FLUA-M1), only crystal structures of its N-terminal domain are available. Here we report the crystal structure of the full-length M1 from another orthomyxovirus that infects fish, the infectious salmon anemia virus (ISAV). The structure of ISAV-M1 assumes the shape of an elbow, with its N domain closely resembling that of the FLUA-M1. The C domain, which is connected to the N domain through a flexible linker, is made of four α-helices packed as a tight bundle. In the crystal, ISAV-M1 monomers form infinite 2D arrays with a network of interactions involving both the N and C domains. Results from liposome flotation assays indicated that ISAV-M1 binds membrane via electrostatic interactions that are primarily mediated by a positively charged surface loop from the N domain. Cryoelectron tomography reconstruction of intact ISA virions identified a matrix protein layer adjacent to the inner leaflet of the viral membrane. The physical dimensions of the virion-associated matrix layer are consistent with the 2D ISAV-M1 crystal lattice, suggesting that the crystal lattice is a valid model for studying M1-M1, M1-membrane, and M1-RNP interactions in the virion.ll members of the Orthomyxoviridae family, including the influenza viruses A-D, thogotovirus, and isavirus, encode a matrix protein called M1. In the influenza A virus, M1 is produced by a colinear transcript made from the gene segment 7 (1). As one of the most abundantly made viral proteins, the influenza A virus M1 plays multiple roles during the virus life cycle. Upon viral entry, the acidification of the viral interior in the endosome weakens the interaction between M1 and the viral ribonucleoprotein complexes (vRNPs), thus allowing M1-free vRNPs to be imported to the nucleus for viral RNA replication and transcription (2, 3). As infection proceeds, newly synthesized M1 enters the nucleus to mediate the nuclear export of nascent vRNPs. A "daisy-chain" complex is formed with the vRNP binding to the C-terminal domain of M1 (4) and the N-terminal domain of M1 interacting with the nuclear export protein (NEP), also called NS2. Through its nuclear export signal (NES), NEP is specifically recognized by the cellular exportin Crm1, which then facilitates the transport of vRNPs across the nuclear membrane to the cytoplasm in a RanGTP-dependent manner (5). It has been shown that M1 binding to vRNP in the nucleus is able to block mRNA transcription (4, 6). In the cytosol, M1 interacts with the cytoplasmic tails of the glycoproteins HA and NA. Such interactions promote M1 association with lipid raft membranes and t...

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“…Thus, BAI1 was known as one of the orphan receptors whose ligand was not identified. During death processes of normal cells, apoptotic cells undergo surface changes, like the exposure of PtdSer on the outer leaflet of their plasma membrane [34]. Phagocytic cells recognize the exposed PtdSer on apoptotic cells and then engulf them [35].…”

Section: Brain-specific Angiogenesis Inhibitors As Engulfment Recementioning

confidence: 99%

Understanding the Role of the BAI Subfamily of Adhesion G Protein-Coupled Receptors (GPCRs) in Pathological and Physiological Conditions

Moon

Shin

et al. 2018

Genes

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Brain-specific angiogenesis inhibitors (BAIs) 1, 2, and 3 are members of the adhesion G protein-coupled receptors, subfamily B, which share a conserved seven-transmembrane structure and an N-terminal extracellular domain. In cell- and animal-based studies, these receptors have been shown to play diverse roles under physiological and pathological conditions. BAI1 is an engulfment receptor and performs major functions in apoptotic-cell clearance and interacts (as a pattern recognition receptor) with pathogen components. BAI1 and -3 also participate in myoblast fusion. Furthermore, BAI1–3 have been linked to tumor progression and neurological diseases. In this review, we summarize the current understanding of the functions of BAI1–3 in pathological and physiological conditions and discuss future directions in terms of the importance of BAIs as pharmacological targets in diseases.

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Programmed cell clearance: From nematodes to humans

Cited by 19 publications

References 79 publications

Three cell deaths and a funeral: macrophage clearance of cells undergoing distinct modes of cell death

Three cell deaths and a funeral: macrophage clearance of cells undergoing distinct modes of cell death

The crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association

Understanding the Role of the BAI Subfamily of Adhesion G Protein-Coupled Receptors (GPCRs) in Pathological and Physiological Conditions

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