Engulfment pathways promote programmed cell death by enhancing the unequal segregation of apoptotic potential

Chakraborty, Sayantan; Lambie, Eric J.; Mikeladze-Dvali, Tamara; Conradt, Barbara

doi:10.1038/ncomms10126

Cited by 37 publications

(55 citation statements)

References 52 publications

(88 reference statements)

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“…In embryos, we often found an enrichment of GFP signal within the apoptotic corpses compared with the surrounding cells (Fig. 1B), consistent with two previous studies (Maurer et al 2007;Chakraborty et al 2015). In the germline, CED-3::GFP was expressed primarily in the oocyte region, with very weak to no expression in the mitotic and early meiotic zones.…”

Section: Resultssupporting

confidence: 91%

Post-transcriptional control of executioner caspases by RNA-binding proteins

et al. 2016

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Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)-PUF-8, MEX-3, GLD-1, and CGH-1-that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3 ′ untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3 ′ UTRs in many metazoans, translational control of executioner caspases by RBPs might be a strategy used widely across the animal kingdom to control apoptosis.

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Section: Resultssupporting

confidence: 91%

Post-transcriptional control of executioner caspases by RNA-binding proteins

et al. 2016

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“…We recently showed that, in the NSM lineage, EGL-1 activity is already present at a certain level in the NSM neuroblast and that this activity is necessary for cellular polarization of the NSM neuroblast and the segregation of apoptotic potential into the daughter that is programmed to die (for review, see Chakraborty et al 2015;Lambie and Conradt 2016). Although we have not yet established that egl-1 is necessary for cellular polarization in ABalappaap, we suggest that the copy number of egl-1 mRNA needs to be kept not only below the threshold sufficient to trigger the mother's death but also above the threshold necessary to cause cellular polarization.…”

Section: Mothers and Sisters Of Cells Normally Programmed To Die Undementioning

confidence: 99%

miRNAs cooperate in apoptosis regulation during C. elegans development

et al. 2017

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Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene egl-1, which encodes a proapoptotic BH3-only protein. In addition, we present evidence that repression of egl-1 is dependent on binding sites for miR-35 and miR-58 family miRNAs within the egl-1 3 ′ untranslated region (UTR), which affect both mRNA copy number and translation. Furthermore, using single-molecule RNA fluorescent in situ hybridization (smRNA FISH), we show that egl-1 is transcribed in the mother of a cell programmed to die and that miR-35 and miR-58 family miRNAs prevent this mother from dying by keeping the copy number of egl-1 mRNA below a critical threshold. Finally, miR-35 and miR-58 family miRNAs can also dampen the transcriptional boost of egl-1 that occurs specifically in a daughter cell that is programmed to die. We propose that miRNAs compensate for lineagespecific differences in egl-1 transcriptional activation, thus ensuring that EGL-1 activity reaches the threshold necessary to trigger death only in daughter cells that are programmed to die.

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“…14,15 More recently, it has been shown that a surrounding phagocytic cell affects caspase levels and activity in the precursor of a dying cell. 16 In another recent example in C. elegans, the engulfment machinery was found to be completely required for the death of a specific cell in the male tail. 17 However, these cases are examples of assisted suicide, as the cell deaths are ultimately dependent on the apoptotic machinery in the dying cell.…”

Section: Introductionmentioning

confidence: 99%

Control of non-apoptotic nurse cell death by engulfment genes in Drosophila

Timmons

Mondragon

Meehan

et al. 2016

Fly

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Programmed cell death occurs as a normal part of oocyte development in Drosophila. For each egg that is formed, 15 germline-derived nurse cells transfer their cytoplasmic contents into the oocyte and die. Disruption of apoptosis or autophagy only partially inhibits the death of the nurse cells, indicating that other mechanisms significantly contribute to nurse cell death. Recently, we demonstrated that the surrounding stretch follicle cells non-autonomously promote nurse cell death during late oogenesis and that phagocytosis genes including draper, ced-12, and the JNK pathway are crucial for this process. When phagocytosis genes are inhibited in the follicle cells, events specifically associated with death of the nurse cells are impaired. Death of the nurse cells is not completely blocked in draper mutants, suggesting that other engulfment receptors are involved. Indeed, we found that the integrin subunit, aPS3, is enriched on stretch follicle cells during late oogenesis and is required for elimination of the nurse cells. Moreover, double mutant analysis revealed that integrins act in parallel to draper. Death of nurse cells in the Drosophila ovary is a unique example of programmed cell death that is both non-apoptotic and non-cell autonomously controlled.

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Engulfment pathways promote programmed cell death by enhancing the unequal segregation of apoptotic potential

Cited by 37 publications

References 52 publications

Post-transcriptional control of executioner caspases by RNA-binding proteins

Post-transcriptional control of executioner caspases by RNA-binding proteins

miRNAs cooperate in apoptosis regulation during C. elegans development

Control of non-apoptotic nurse cell death by engulfment genes in Drosophila

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