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Biochem Biophys Res Commun,
2017]
Programmed cell clearance is a highly regulated physiological process of elimination of dying cells that occurs rapidly and efficiently in healthy organisms. It thus ensures proper development as well as homeostasis. Recent studies have disclosed a considerable degree of conservation of cell clearance pathways between nematodes and higher organisms. The externalization of the anionic phospholipid phosphatidylserine (PS) has emerged as an important "eat-me" signal for phagocytes and its exposition on apoptotic cells is controlled by phospholipid translocases and scramblases. However, there is mounting evidence that PS exposure occurs not only in apoptosis, but may also be actively expressed on the surface of cells undergoing other forms of cell death including necrosis; PS is also expressed on the surface of engulfing cells. Additionally, PS may act as a "save-me" signal during axonal regeneration. Here we discuss mechanisms of PS exposure and its recognition by phagocytes as well as the consequences of PS signaling in nematodes and in mammals.
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Methods Cell Biol,
1995]
Both the localization and distribution of nucleic acid sequences in genomes and in cells can be visualized by hybridization of labeled probe DNAs to cytological preparations of chromosomes or tissues. With the introduction of nonisotopically labeled nucleotides that could be incorporated into cloned DNAs by enzymatic methods in vitro, it became possible to detect the site of hybridization quickly using antibodies that recognized the modifying group on the nucleotides incorporated into the probe DNA. More recently, nucleotides labeled with a fluorescent molecule have been incorporated into probes by invitro enzymatic reactions and the site of hybridization can then be visualized directly. As fluorescence in situ hybridization provides a rapid and high-resolution method for mapping genes, it is being sued increasingly for mapping cloned DNAs to chromosomes and for the ordering of clones in large-scale genome projects. On the other hand, physically mapped clones can also be used to label chromosomes for analysis of such biological processes as chromosome segregation, pairing in meiosis, and interphase nuclear order. Nonisotopic methods of hybridization are also ideally suited to visualization of mRNA distributions in tissues, because the signal can be detected in thick specimens, in contrast to isotopic methods that require thin specimens for detection by autoradiography...
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Front Cell Dev Biol,
2023]
Phosphatidylserine (PS) is a lipid component of the plasma membrane. It is asymmetrically distributed to the inner leaflet in live cells. In cells undergoing apoptosis, phosphatidylserine is exposed to the outer surfaces. The exposed phosphatidylserine acts as an evolutionarily conserved "eat-me" signal that attracts neighboring engulfing cells in metazoan organisms, including the nematode <i>Caenorhabditis elegans</i>, the fruit fly <i>Drosophila melanogaster</i>, and mammals. During apoptosis, the exposure of phosphatidylserine to the outer surface of a cell is driven by the membrane scramblases and flippases, the activities of which are regulated by caspases. Cells undergoing necrosis, a kind of cell death frequently associated with cellular injuries and morphologically distinct from apoptosis, were initially believed to allow passive exposure of phosphatidylserine through membrane rupture. Later studies revealed that necrotic cells actively expose phosphatidylserine before any rupture occurs. A recent study in <i>C. elegans</i> further reported that the calcium ion (Ca<sup>2+</sup>) plays an essential role in promoting the exposure of phosphatidylserine on the surfaces of necrotic cells. These findings indicate that necrotic and apoptotic cells, which die through different molecular mechanisms, use common and unique mechanisms for promoting the exposure of the same "eat me" signal. This article will review the mechanisms regulating the exposure of phosphatidylserine on the surfaces of necrotic and apoptotic cells and highlight their similarities and differences.
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Front Immunol,
2017]
For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells). Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin -PS3/-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes.