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Programmed cell death and clearance of cell corpses in Caenorhabditis elegans

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Abstract

Programmed cell death is critical to the development of diverse animal species from C. elegans to humans. In C. elegans, the cell death program has three genetically distinguishable phases. During the cell suicide phase, the core cell death machinery is activated through a protein interaction cascade. This activates the caspase CED-3, which promotes numerous pro-apoptotic activities including DNA degradation and exposure of the phosphatidylserine “eat me” signal on the cell corpse surface. Specification of the cell death fate involves transcriptional activation of the cell death initiator EGL-1 or the caspase CED-3 by coordinated actions of specific transcription factors in distinct cell types. In the cell corpse clearance stage, recognition of cell corpses by phagocytes triggers several signaling pathways to induce phagocytosis of apoptotic cell corpses. Cell corpse-enclosing phagosomes ultimately fuse with lysosomes for digestion of phagosomal contents. This article summarizes our current knowledge about programmed cell death and clearance of cell corpses in C. elegans.

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References

  1. Lettre G, Hengartner MO (2006) Developmental apoptosis in C. elegans: a complex CEDnario. Nat Rev Mol Cell Biol 7(2):97–108

    Article  CAS  PubMed  Google Scholar 

  2. Sulston JE, Horvitz HR (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56(1):110–156

    Article  CAS  PubMed  Google Scholar 

  3. Sulston JE, Schierenberg E, White JG, Thomson JN (1983) The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100(1):64–119

    Article  CAS  PubMed  Google Scholar 

  4. Gumienny TL, Lambie E, Hartwieg E, Horvitz HR, Hengartner MO (1999) Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development 126(5):1011–1022

    CAS  PubMed  Google Scholar 

  5. Gartner A, Milstein S, Ahmed S, Hodgkin J, Hengartner MO (2000) A conserved checkpoint pathway mediates DNA damage–induced apoptosis and cell cycle arrest in C. elegans. Mol Cell 5(3):435–443

    Article  CAS  PubMed  Google Scholar 

  6. Conradt B, Xue D (2005) Programmed cell death. WormBook: the online review of C. elegans biology, pp 1–13

  7. Horvitz HR (1999) Genetic control of programmed cell death in the nematode Caenorhabditis elegans. Cancer Res 59(7 Suppl):1701s–1706s

    CAS  PubMed  Google Scholar 

  8. Horvitz HR (2003) Nobel lecture. Worms, life and death. Biosci Rep 23(5–6):239–303

    Article  CAS  PubMed  Google Scholar 

  9. Conradt B, Horvitz HR (1998) The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93(4):519–529

    Article  CAS  PubMed  Google Scholar 

  10. Ellis HM, Horvitz HR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44(6):817–829. pii: 0092-8674(86)90004-8

  11. Hengartner MO, Ellis RE, Horvitz HR (1992) Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356(6369):494–499

    Article  CAS  PubMed  Google Scholar 

  12. Shaham S, Horvitz HR (1996) Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities. Genes Dev 10(5):578–591

    Article  CAS  PubMed  Google Scholar 

  13. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75(4):641–652

    Article  CAS  PubMed  Google Scholar 

  14. Xue D, Shaham S, Horvitz HR (1996) The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease. Genes Dev 10(9):1073–1083

    Article  CAS  PubMed  Google Scholar 

  15. Yuan J, Horvitz HR (1992) The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Development 116(2):309–320

    CAS  PubMed  Google Scholar 

  16. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90(3):405–413

    Article  CAS  PubMed  Google Scholar 

  17. Hengartner MO, Horvitz HR (1994) C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell 76(4):665–676

    Article  CAS  PubMed  Google Scholar 

  18. Chinnaiyan AM, O’Rourke K, Lane BR, Dixit VM (1997) Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science 275(5303):1122–1126

    Article  CAS  PubMed  Google Scholar 

  19. Wu D, Wallen HD, Nunez G (1997) Interaction and regulation of subcellular localization of CED-4 by CED-9. Science 275(5303):1126–1129

    Article  CAS  PubMed  Google Scholar 

  20. Spector MS, Desnoyers S, Hoeppner DJ, Hengartner MO (1997) Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature 385(6617):653–656. doi:10.1038/385653a0

    Article  CAS  PubMed  Google Scholar 

  21. Parrish J, Metters H, Chen L, Xue D (2000) Demonstration of the in vivo interaction of key cell death regulators by structure-based design of second-site suppressors. Proc Natl Acad Sci USA 97(22):11916–11921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. del Peso L, Gonzalez VM, Nunez G (1998) Caenorhabditis elegans EGL-1 disrupts the interaction of CED-9 with CED-4 and promotes CED-3 activation. J Biol Chem 273(50):33495–33500

    Article  CAS  PubMed  Google Scholar 

  23. Chen F, Hersh BM, Conradt B, Zhou Z, Riemer D, Gruenbaum Y, Horvitz HR (2000) Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death. Science 287(5457):1485-1489. pii: 8293

  24. Yan N, Chai J, Lee ES, Gu L, Liu Q, He J, Wu JW, Kokel D, Li H, Hao Q, Xue D, Shi Y (2005) Structure of the CED-4–CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans. Nature 437(7060):831–837

    Article  CAS  PubMed  Google Scholar 

  25. Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y (2004) Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol Cell 15(6):999–1006

    Article  CAS  PubMed  Google Scholar 

  26. Qi S, Pang Y, Hu Q, Liu Q, Li H, Zhou Y, He T, Liang Q, Liu Y, Yuan X, Luo G, Li H, Wang J, Yan N, Shi Y (2010) Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell 141(3):446–457. doi:10.1016/j.cell.2010.03.017

    Article  CAS  PubMed  Google Scholar 

  27. Huang W, Jiang T, Choi W, Qi S, Pang Y, Hu Q, Xu Y, Gong X, Jeffrey PD, Wang J, Shi Y (2013) Mechanistic insights into CED-4-mediated activation of CED-3. Genes Dev 27(18):2039–2048. doi:10.1101/gad.224428.113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shen Q, Qin F, Gao Z, Cui J, Xiao H, Xu Z, Yang C (2009) Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans. Mol Cell Biol 29(14):3881–3893. doi:10.1128/MCB.01509-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shaham S, Horvitz HR (1996) An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor. Cell 86(2):201–208

    Article  CAS  PubMed  Google Scholar 

  30. Galvin BD, Denning DP, Horvitz HR (2011) SPK-1, an SR protein kinase, inhibits programmed cell death in Caenorhabditis elegans. Proc Natl Acad Sci USA 108(5):1998–2003. doi:10.1073/pnas.1018805108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chiorazzi M, Rui L, Yang Y, Ceribelli M, Tishbi N, Maurer CW, Ranuncolo SM, Zhao H, Xu W, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Shaham S, Staudt LM (2013) Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proc Natl Acad Sci USA 110(10):3943–3948. doi:10.1073/pnas.1217271110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hirose T, Horvitz HR (2014) The translational regulators GCN-1 and ABCF-3 act together to promote apoptosis in C. elegans. PLoS Genet 10(8):e1004512. doi:10.1371/journal.pgen.1004512

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Huang CY, Chen JY, Wu SC, Tan CH, Tzeng RY, Lu PJ, Wu YF, Chen RH, Wu YC (2012) C. elegans EIF-3.K promotes programmed cell death through CED-3 caspase. PLoS One 7(5):e36584. doi:10.1371/journal.pone.0036584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xue D, Horvitz HR (1997) Caenorhabditis elegans CED-9 protein is a bifunctional cell-death inhibitor. Nature 390(6657):305–308. doi:10.1038/36889

    Article  CAS  PubMed  Google Scholar 

  35. Nakagawa A, Shi Y, Kage-Nakadai E, Mitani S, Xue D (2010) Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease. Science 328(5976):327–334. doi:10.1126/science.1182374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ge X, Zhao X, Nakagawa A, Gong X, Skeen-Gaar RR, Shi Y, Gong H, Wang X, Xue D (2014) A novel mechanism underlies caspase-dependent conversion of the dicer ribonuclease into a deoxyribonuclease during apoptosis. Cell Res 24(2):218–232. doi:10.1038/cr.2013.160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chen YZ, Mapes J, Lee ES, Skeen-Gaar RR, Xue D (2013) Caspase-mediated activation of Caenorhabditis elegans CED-8 promotes apoptosis and phosphatidylserine externalization. Nat Commun 4:2726. doi:10.1038/ncomms3726

    PubMed  PubMed Central  Google Scholar 

  38. Breckenridge DG, Kang BH, Kokel D, Mitani S, Staehelin LA, Xue D (2008) Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution pathways downstream of ced-3 and independent of ced-9. Mol Cell 31(4):586–597. doi:10.1016/j.molcel.2008.07.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nakagawa A, Sullivan KD, Xue D (2014) Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis by inhibiting the AKT pathway. Nat Struct Mol Biol 21(12):1082–1090. doi:10.1038/nsmb.2915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Shaham S (1998) Identification of multiple Caenorhabditis elegans caspases and their potential roles in proteolytic cascades. J Biol Chem 273(52):35109–35117

    Article  CAS  PubMed  Google Scholar 

  41. Denning DP, Hatch V, Horvitz HR (2013) Both the caspase CSP-1 and a caspase-independent pathway promote programmed cell death in parallel to the canonical pathway for apoptosis in Caenorhabditis elegans. PLoS Genet 9(3):e1003341. doi:10.1371/journal.pgen.1003341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Geng X, Shi Y, Nakagawa A, Yoshina S, Mitani S, Shi Y, Xue D (2008) Inhibition of CED-3 zymogen activation and apoptosis in Caenorhabditis elegans by caspase homolog CSP-3. Nat Struct Mol Biol 15(10):1094–1101. doi:10.1038/nsmb.1488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Geng X, Zhou QH, Kage-Nakadai E, Shi Y, Yan N, Mitani S, Xue D (2009) Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 autoactivation and apoptosis in germ cells. Cell Death Differ 16(10):1385–1394. doi:10.1038/cdd.2009.88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Liu X, Li P, Widlak P, Zou H, Luo X, Garrard WT, Wang X (1998) The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis. Proc Natl Acad Sci USA 95(15):8461–8466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391(6662):43–50. doi:10.1038/34112

    Article  CAS  PubMed  Google Scholar 

  46. Liu X, Zou H, Widlak P, Garrard W, Wang X (1999) Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease). Oligomerization and direct interaction with histone H1. J Biol Chem 274(20):13836–13840

    Article  CAS  PubMed  Google Scholar 

  47. Sakahira H, Enari M, Nagata S (1998) Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391(6662):96–99. doi:10.1038/34214

    Article  CAS  PubMed  Google Scholar 

  48. Parrish J, Li L, Klotz K, Ledwich D, Wang X, Xue D (2001) Mitochondrial endonuclease G is important for apoptosis in C. elegans. Nature 412(6842):90–94

    Article  CAS  PubMed  Google Scholar 

  49. Parrish JZ, Xue D (2003) Functional genomic analysis of apoptotic DNA degradation in C. elegans. Mol Cell 11(4):987–996

    Article  CAS  PubMed  Google Scholar 

  50. Parrish JZ, Yang C, Shen B, Xue D (2003) CRN-1, a Caenorhabditis elegans FEN-1 homologue, cooperates with CPS-6/EndoG to promote apoptotic DNA degradation. EMBO J 22(13):3451–3460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wang X, Yang C, Chai J, Shi Y, Xue D (2002) Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science 298(5598):1587–1592

    Article  CAS  PubMed  Google Scholar 

  52. Wu YC, Stanfield GM, Horvitz HR (2000) NUC-1, a Caenorhabditis elegans DNase II homolog, functions in an intermediate step of DNA degradation during apoptosis. Genes Dev 14(5):536–548

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Conradt B (2009) Genetic control of programmed cell death during animal development. Annu Rev Genet 43:493–523. doi:10.1146/annurev.genet.42.110807.091533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Peden E, Killian DJ, Xue D (2008) Cell death specification in C. elegans. Cell cycle 7(16):2479–2484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Jiang HS, Wu YC (2014) LIN-3/EGF promotes the programmed cell death of specific cells in Caenorhabditis elegans by transcriptional activation of the pro-apoptotic gene egl-1. PLoS genetics 10(8):e1004513. doi:10.1371/journal.pgen.1004513

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Thellmann M, Hatzold J, Conradt B (2003) The Snail-like CES-1 protein of C. elegans can block the expression of the BH3-only cell-death activator gene egl-1 by antagonizing the function of bHLH proteins. Development 130(17):4057–4071

    Article  CAS  PubMed  Google Scholar 

  57. Metzstein MM, Hengartner MO, Tsung N, Ellis RE, Horvitz HR (1996) Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2. Nature 382(6591):545–547. doi:10.1038/382545a0

    Article  CAS  PubMed  Google Scholar 

  58. Metzstein MM, Horvitz HR (1999) The C. elegans cell death specification gene ces-1 encodes a snail family zinc finger protein. Mol Cell 4(3):309–319. pii: S1097-2765(00)80333-0

  59. Hatzold J, Conradt B (2008) Control of apoptosis by asymmetric cell division. PLoS Biol 6(4):e84. doi:10.1371/journal.pbio.0060084

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Hirose T, Horvitz HR (2013) An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways. Nature 500(7462):354–358. doi:10.1038/nature12329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Cordes S, Frank CA, Garriga G (2006) The C. elegans MELK ortholog PIG-1 regulates cell size asymmetry and daughter cell fate in asymmetric neuroblast divisions. Development 133(14):2747–2756. doi:10.1242/dev.02447

    Article  CAS  PubMed  Google Scholar 

  62. Gurling M, Talavera K, Garriga G (2014) The DEP domain-containing protein TOE-2 promotes apoptosis in the Q lineage of C. elegans through two distinct mechanisms. Development 141(13):2724–2734. doi:10.1242/dev.110486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Teuliere J, Cordes S, Singhvi A, Talavera K, Garriga G (2014) Asymmetric neuroblast divisions producing apoptotic cells require the cytohesin GRP-1 in Caenorhabditis elegans. Genetics 198(1):229–247. doi:10.1534/genetics.114.167189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Singhvi A, Teuliere J, Talavera K, Cordes S, Ou G, Vale RD, Prasad BC, Clark SG, Garriga G (2011) The Arf GAP CNT-2 regulates the apoptotic fate in C. elegans asymmetric neuroblast divisions. Curr Biol 21(11):948–954. doi:10.1016/j.cub.2011.04.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Conradt B, Horvitz HR (1999) The TRA-1A sex determination protein of C. elegans regulates sexually dimorphic cell deaths by repressing the egl-1 cell death activator gene. Cell 98(3):317–327

    Article  CAS  PubMed  Google Scholar 

  66. Starostina NG, Lim JM, Schvarzstein M, Wells L, Spence AM, Kipreos ET (2007) A CUL-2 ubiquitin ligase containing three FEM proteins degrades TRA-1 to regulate C. elegans sex determination. Dev Cell 13(1):127–139. doi:10.1016/j.devcel.2007.05.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zarkower D (2006) Somatic sex determination. WormBook: the online review of C. elegans biology, pp 1–12. doi:10.1895/wormbook.1.84.1

  68. Jager S, Schwartz HT, Horvitz HR, Conradt B (2004) The Caenorhabditis elegans F-box protein SEL-10 promotes female development and may target FEM-1 and FEM-3 for degradation by the proteasome. Proc Natl Acad Sci USA 101(34):12549–12554. doi:10.1073/pnas.0405087101

    Article  PubMed  PubMed Central  Google Scholar 

  69. Peden E, Kimberly E, Gengyo-Ando K, Mitani S, Xue D (2007) Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-37/Groucho. Genes Dev 21(23):3195–3207. doi:10.1101/gad.1607807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Schwartz HT, Horvitz HR (2007) The C. elegans protein CEH-30 protects male-specific neurons from apoptosis independently of the Bcl-2 homolog CED-9. Genes Dev 21(23):3181–3194. doi:10.1101/gad.1607007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Liu H, Strauss TJ, Potts MB, Cameron S (2006) Direct regulation of egl-1 and of programmed cell death by the Hox protein MAB-5 and by CEH-20, a C. elegans homolog of Pbx1. Development 133(4):641–650. doi:10.1242/dev.02234

    Article  CAS  PubMed  Google Scholar 

  72. Wang J, Chitturi J, Ge Q, Laskova V, Wang W, Li X, Ding M, Zhen M, Huang X (2015) The C. elegans COE transcription factor UNC-3 activates lineage-specific apoptosis and affects neurite growth in the RID lineage. Development 142(8):1447–1457. doi:10.1242/dev.119479

    Article  CAS  PubMed  Google Scholar 

  73. Hirose T, Galvin BD, Horvitz HR (2010) Six and Eya promote apoptosis through direct transcriptional activation of the proapoptotic BH3-only gene egl-1 in Caenorhabditis elegans. Proc Natl Acad Sci USA 107(35):15479–15484. doi:10.1073/pnas.1010023107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Maurer CW, Chiorazzi M, Shaham S (2007) Timing of the onset of a developmental cell death is controlled by transcriptional induction of the C. elegans ced-3 caspase-encoding gene. Development 134(7):1357–1368. doi:10.1242/dev.02818

    Article  CAS  PubMed  Google Scholar 

  75. Kritikou EA, Milstein S, Vidalain PO, Lettre G, Bogan E, Doukoumetzidis K, Gray P, Chappell TG, Vidal M, Hengartner MO (2006) C. elegans GLA-3 is a novel component of the MAP kinase MPK-1 signaling pathway required for germ cell survival. Genes Dev 20(16):2279–2292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lettre G, Kritikou EA, Jaeggi M, Calixto A, Fraser AG, Kamath RS, Ahringer J, Hengartner MO (2004) Genome-wide RNAi identifies p53-dependent and -independent regulators of germ cell apoptosis in C. elegans. Cell Death Differ 11(11):1198–1203

    Article  CAS  PubMed  Google Scholar 

  77. Schertel C, Conradt B (2007) C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions. Development 134(20):3691–3701. doi:10.1242/dev.004606

    Article  CAS  PubMed  Google Scholar 

  78. Park D, Jia H, Rajakumar V, Chamberlin HM (2006) Pax2/5/8 proteins promote cell survival in C. elegans. Development 133(21):4193–4202. doi:10.1242/dev.02614

    Article  CAS  PubMed  Google Scholar 

  79. Derry WB, Putzke AP, Rothman JH (2001) Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance. Science 294(5542):591–595

    Article  CAS  PubMed  Google Scholar 

  80. Schumacher B, Hofmann K, Boulton S, Gartner A (2001) The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis. Curr Biol 11(21):1722–1727

    Article  CAS  PubMed  Google Scholar 

  81. Schumacher B, Schertel C, Wittenburg N, Tuck S, Mitani S, Gartner A, Conradt B, Shaham S (2005) C. elegans ced-13 can promote apoptosis and is induced in response to DNA damage. Cell Death Differ 12(2):153–161

    Article  CAS  PubMed  Google Scholar 

  82. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288(5468):1053–1058

    Article  CAS  PubMed  Google Scholar 

  83. Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B (2001) PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell 7(3):673–682

    Article  CAS  PubMed  Google Scholar 

  84. Gartner A, Boag PR, Blackwell TK (2008) Germline survival and apoptosis. WormBook: the online review of C. elegans biology, pp 1–20

  85. Schumacher B, Hanazawa M, Lee MH, Nayak S, Volkmann K, Hofmann ER, Hengartner M, Schedl T, Gartner A (2005) Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. Cell 120(3):357–368

    Article  CAS  PubMed  Google Scholar 

  86. Yang M, Sun J, Sun X, Shen Q, Gao Z, Yang C (2009) Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis. PLoS Genet 5(6):e1000514

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Greiss S, Hall J, Ahmed S, Gartner A (2008) C. elegans SIR-2.1 translocation is linked to a proapoptotic pathway parallel to cep-1/p53 during DNA damage-induced apoptosis. Genes Dev 22(20):2831–2842. doi:10.1101/gad.482608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xu J, Sun X, Jing Y, Wang M, Liu K, Jian Y, Yang M, Cheng Z, Yang C (2012) MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells. Cell Res 22(5):886–902. doi:10.1038/cr.2012.2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Bhalla N, Dernburg AF (2005) A conserved checkpoint monitors meiotic chromosome synapsis in Caenorhabditis elegans. Science 310(5754):1683–1686

    Article  CAS  PubMed  Google Scholar 

  90. Dombecki CR, Chiang AC, Kang HJ, Bilgir C, Stefanski NA, Neva BJ, Klerkx EP, Nabeshima K (2011) The chromodomain protein MRG-1 facilitates SC-independent homologous pairing during meiosis in Caenorhabditis elegans. Dev Cell 21(6):1092–1103. doi:10.1016/j.devcel.2011.09.019

    Article  CAS  PubMed  Google Scholar 

  91. Mei F, Chen PF, Dombecki CR, Aljabban I, Nabeshima K (2015) A defective meiotic outcome of a failure in homologous pairing and synapsis is masked by meiotic quality control. PLoS One 10(8):e0134871. doi:10.1371/journal.pone.0134871

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Denning DP, Hatch V, Horvitz HR (2012) Programmed elimination of cells by caspase-independent cell extrusion in C. elegans. Nature 488 (7410):226-230. doi:10.1038/nature11240

  93. Rosenblatt J (2012) Programmed cell death: a new way worms get rid of unwanted cells. Curr Biol 22(19):R844–R846. doi:10.1016/j.cub.2012.08.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Abraham MC, Lu Y, Shaham S (2007) A morphologically conserved nonapoptotic program promotes linker cell death in Caenorhabditis elegans. Dev Cell 12(1):73–86. doi:10.1016/j.devcel.2006.11.012

    Article  CAS  PubMed  Google Scholar 

  95. Blum ES, Abraham MC, Yoshimura S, Lu Y, Shaham S (2012) Control of nonapoptotic developmental cell death in Caenorhabditis elegans by a polyglutamine-repeat protein. Science 335(6071):970–973. doi:10.1126/science.1215156

    Article  CAS  PubMed  Google Scholar 

  96. Vlachos M, Tavernarakis N (2010) Non-apoptotic cell death in Caenorhabditis elegans. Dev Dyn 239(5):1337–1351. doi:10.1002/dvdy.22230

    Article  CAS  PubMed  Google Scholar 

  97. Reddien PW, Cameron S, Horvitz HR (2001) Phagocytosis promotes programmed cell death in C. elegans. Nature 412(6843):198–202. doi:10.1038/35084096

    Article  CAS  PubMed  Google Scholar 

  98. Hoeppner DJ, Hengartner MO, Schnabel R (2001) Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans. Nature 412(6843):202–206

    Article  CAS  PubMed  Google Scholar 

  99. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148(7):2207–2216

    CAS  PubMed  Google Scholar 

  100. Wang X, Wang J, Gengyo-Ando K, Gu L, Sun CL, Yang C, Shi Y, Kobayashi T, Shi Y, Mitani S, Xie XS, Xue D (2007) C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1. Nat Cell Biol 9(5):541–549

    Article  CAS  PubMed  Google Scholar 

  101. Darland-Ransom M, Wang X, Sun CL, Mapes J, Gengyo-Ando K, Mitani S, Xue D (2008) Role of C. elegans TAT-1 protein in maintaining plasma membrane phosphatidylserine asymmetry. Science 320(5875):528–531

    Article  CAS  PubMed  Google Scholar 

  102. Zullig S, Neukomm LJ, Jovanovic M, Charette SJ, Lyssenko NN, Halleck MS, Reutelingsperger CP, Schlegel RA, Hengartner MO (2007) Aminophospholipid translocase TAT-1 promotes phosphatidylserine exposure during C. elegans apoptosis. Curr Biol 17(11):994–999

    Article  PubMed  CAS  Google Scholar 

  103. Venegas V, Zhou Z (2007) Two alternative mechanisms that regulate the presentation of apoptotic cell engulfment signal in Caenorhabditis elegans. Mol Biol Cell 18(8):3180–3192. doi:10.1091/mbc.E07-02-0138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Suzuki J, Denning DP, Imanishi E, Horvitz HR, Nagata S (2013) Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science 341(6144):403–406. doi:10.1126/science.1236758

    Article  CAS  PubMed  Google Scholar 

  105. Li Z, Venegas V, Nagaoka Y, Morino E, Raghavan P, Audhya A, Nakanishi Y, Zhou Z (2015) Necrotic cells actively attract phagocytes through the collaborative action of two distinct PS-exposure mechanisms. PLoS Genet 11(6):e1005285. doi:10.1371/journal.pgen.1005285

    Article  PubMed  PubMed Central  Google Scholar 

  106. Zhou Z, Hartwieg E, Horvitz HR (2001) CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 104(1):43–56. pii :S0092-8674(01)00190-8

  107. Wang X, Li W, Zhao D, Liu B, Shi Y, Chen B, Yang H, Guo P, Geng X, Shang Z, Peden E, Kage-Nakadai E, Mitani S, Xue D (2010) Caenorhabditis elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor. Nat Cell Biol 12(7):655–664

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Kang Y, Zhao D, Liang H, Liu B, Zhang Y, Liu Q, Wang X, Liu Y (2012) Structural study of TTR-52 reveals the mechanism by which a bridging molecule mediates apoptotic cell engulfment. Genes Dev 26(12):1339–1350. doi:10.1101/gad.187815.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Wu YC, Horvitz HR (1998) The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters. Cell 93(6):951–960. pii: S0092-8674(00)81201-5

  110. Callahan MK, Williamson P, Schlegel RA (2000) Surface expression of phosphatidylserine on macrophages is required for phagocytosis of apoptotic thymocytes. Cell Death Differ 7(7):645–653. doi:10.1038/sj.cdd.4400690

    Article  CAS  PubMed  Google Scholar 

  111. Callahan MK, Halleck MS, Krahling S, Henderson AJ, Williamson P, Schlegel RA (2003) Phosphatidylserine expression and phagocytosis of apoptotic thymocytes during differentiation of monocytic cells. J Leukoc Biol 74(5):846–856. doi:10.1189/jlb.0902433

    Article  CAS  PubMed  Google Scholar 

  112. Marguet D, Luciani MF, Moynault A, Williamson P, Chimini G (1999) Engulfment of apoptotic cells involves the redistribution of membrane phosphatidylserine on phagocyte and prey. Nat Cell Biol 1(7):454–456. doi:10.1038/15690

    Article  CAS  PubMed  Google Scholar 

  113. Zhang Y, Wang H, Kage-Nakadai E, Mitani S, Wang X (2012) C. elegans secreted lipid-binding protein NRF-5 mediates PS appearance on phagocytes for cell corpse engulfment. Curr Biol 22(14):1276–1284. doi:10.1016/j.cub.2012.06.004

    Article  PubMed  CAS  Google Scholar 

  114. Mapes J, Chen YZ, Kim A, Mitani S, Kang BH, Xue D (2012) CED-1, CED-7, and TTR-52 regulate surface phosphatidylserine expression on apoptotic and phagocytic cells. Curr Biol 22(14):1267–1275. doi:10.1016/j.cub.2012.05.052

    Article  CAS  PubMed  Google Scholar 

  115. Yang H, Chen YZ, Zhang Y, Wang X, Zhao X, Godfroy JI 3rd, Liang Q, Zhang M, Zhang T, Yuan Q, Ann Royal M, Driscoll M, Xia NS, Yin H, Xue D (2015) A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells. Nat Commun 6:5717. doi:10.1038/ncomms6717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Wang X, Wu YC, Fadok VA, Lee MC, Gengyo-Ando K, Cheng LC, Ledwich D, Hsu PK, Chen JY, Chou BK, Henson P, Mitani S, Xue D (2003) Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Science 302(5650):1563–1566

    Article  CAS  PubMed  Google Scholar 

  117. Neumann B, Coakley S, Giordano-Santini R, Linton C, Lee ES, Nakagawa A, Xue D, Hilliard MA (2015) EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature 517(7533):219–222. doi:10.1038/nature14102

    Article  CAS  PubMed  Google Scholar 

  118. Hsu TY, Wu YC (2010) Engulfment of apoptotic cells in C. elegans is mediated by integrin alpha/SRC signaling. Curr Biol 20(6):477–486. doi:10.1016/j.cub.2010.01.062

    Article  CAS  PubMed  Google Scholar 

  119. Hsieh HH, Hsu TY, Jiang HS, Wu YC (2012) Integrin alpha PAT-2/CDC-42 signaling is required for muscle-mediated clearance of apoptotic cells in Caenorhabditis elegans. PLoS Genet 8(5):e1002663. doi:10.1371/journal.pgen.1002663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Cabello J, Neukomm LJ, Gunesdogan U, Burkart K, Charette SJ, Lochnit G, Hengartner MO, Schnabel R (2010) The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac. PLoS Biol 8(2):e1000297. doi:10.1371/journal.pbio.1000297

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, Nishiwaki K, Walk SF, Nemergut ME, Macara IG, Francis R, Schedl T, Qin Y, Van Aelst L, Hengartner MO, Ravichandran KS (2001) CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 107(1):27–41

    Article  CAS  PubMed  Google Scholar 

  122. Wu YC, Tsai MC, Cheng LC, Chou CJ, Weng NY (2001) C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment. Dev Cell 1(4):491–502

    Article  CAS  PubMed  Google Scholar 

  123. Zhou Z, Caron E, Hartwieg E, Hall A, Horvitz HR (2001) The C. elegans PH domain protein CED-12 regulates cytoskeletal reorganization via a Rho/Rac GTPase signaling pathway. Dev Cell 1(4):477–489

    Article  CAS  PubMed  Google Scholar 

  124. Wu YC, Horvitz HR (1998) C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 392(6675):501–504. doi:10.1038/33163

    Article  CAS  PubMed  Google Scholar 

  125. Reddien PW, Horvitz HR (2000) CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat Cell Biol 2(3):131–136

    Article  CAS  PubMed  Google Scholar 

  126. deBakker CD, Haney LB, Kinchen JM, Grimsley C, Lu M, Klingele D, Hsu PK, Chou BK, Cheng LC, Blangy A, Sondek J, Hengartner MO, Wu YC, Ravichandran KS (2004) Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. Curr Biol 14(24):2208–2216

    Article  CAS  PubMed  Google Scholar 

  127. Liu QA, Hengartner MO (1998) Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C. elegans. Cell 93(6):961–972

    Article  CAS  PubMed  Google Scholar 

  128. Su HP, Nakada-Tsukui K, Tosello-Trampont AC, Li Y, Bu G, Henson PM, Ravichandran KS (2002) Interaction of CED-6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-related protein (LRP). J Biol Chem 277(14):11772–11779

    Article  CAS  PubMed  Google Scholar 

  129. Yu X, Odera S, Chuang CH, Lu N, Zhou Z (2006) C. elegans Dynamin mediates the signaling of phagocytic receptor CED-1 for the engulfment and degradation of apoptotic cells. Dev Cell 10(6):743–757

    Article  CAS  PubMed  Google Scholar 

  130. Chen D, Jian Y, Liu X, Zhang Y, Liang J, Qi X, Du H, Zou W, Chen L, Chai Y, Ou G, Miao L, Wang Y, Yang C (2013) Clathrin and AP2 are required for phagocytic receptor-mediated apoptotic cell clearance in Caenorhabditis elegans. PLoS Genet 9(5):e1003517. doi:10.1371/journal.pgen.1003517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Shen Q, He B, Lu N, Conradt B, Grant BD, Zhou Z (2013) Phagocytic receptor signaling regulates clathrin and epsin-mediated cytoskeletal remodeling during apoptotic cell engulfment in C. elegans. Development 140(15):3230–3243. doi:10.1242/dev.093732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Kinchen JM, Cabello J, Klingele D, Wong K, Feichtinger R, Schnabel H, Schnabel R, Hengartner MO (2005) Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans. Nature 434(7029):93–99

    Article  CAS  PubMed  Google Scholar 

  133. Neukomm LJ, Zeng S, Frei AP, Huegli PA, Hengartner MO (2014) Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans. Cell Death Differ 21(6):845–853. doi:10.1038/cdd.2014.23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Zou W, Lu Q, Zhao D, Li W, Mapes J, Xie Y, Wang X (2009) Caenorhabditis elegans myotubularin MTM-1 negatively regulates the engulfment of apoptotic cells. PLoS Genet 5(10):e1000679

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Neukomm LJ, Nicot AS, Kinchen JM, Almendinger J, Pinto SM, Zeng S, Doukoumetzidis K, Tronchere H, Payrastre B, Laporte JF, Hengartner MO (2011) The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans. Development 138(10):2003–2014. doi:10.1242/dev.060012

    Article  CAS  PubMed  Google Scholar 

  136. Neukomm LJ, Frei AP, Cabello J, Kinchen JM, Zaidel-Bar R, Ma Z, Haney LB, Hardin J, Ravichandran KS, Moreno S, Hengartner MO (2011) Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans. Nat Cell Biol 13(1):79–86. doi:10.1038/ncb2138

    Article  CAS  PubMed  Google Scholar 

  137. Hurwitz ME, Vanderzalm PJ, Bloom L, Goldman J, Garriga G, Horvitz HR (2009) Abl kinase inhibits the engulfment of apopotic cells in Caenorhabditis elegans. PLoS Biol 7(4):e99

    Article  PubMed  CAS  Google Scholar 

  138. Bohdanowicz M, Grinstein S (2013) Role of phospholipids in endocytosis, phagocytosis, and macropinocytosis. Physiol Rev 93(1):69–106. doi:10.1152/physrev.00002.2012

    Article  CAS  PubMed  Google Scholar 

  139. Flannagan RS, Jaumouille V, Grinstein S (2012) The cell biology of phagocytosis. Annu Rev Pathol 7:61–98. doi:10.1146/annurev-pathol-011811-132445

    Article  CAS  PubMed  Google Scholar 

  140. Cheng S, Wang K, Zou W, Miao R, Huang Y, Wang H, Wang X (2015) PtdIns(4,5)P2 and PtdIns3P coordinate to regulate phagosomal sealing for apoptotic cell clearance. J Cell Biol 210(3):485–502. doi:10.1083/jcb.201501038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Almendinger J, Doukoumetzidis K, Kinchen JM, Kaech A, Ravichandran KS, Hengartner MO (2011) A conserved role for SNX9-family members in the regulation of phagosome maturation during engulfment of apoptotic cells. PLoS One 6(4):e18325. doi:10.1371/journal.pone.0018325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Lu N, Shen Q, Mahoney TR, Liu X, Zhou Z (2010) Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling. Mol Biol Cell 22(3):354–374. doi:10.1091/mbc.E10-09-0756

    Article  CAS  Google Scholar 

  143. Lundmark R, Carlsson SR (2009) SNX9—a prelude to vesicle release. J Cell Sci 122(Pt 1):5–11. doi:10.1242/jcs.037135

    Article  CAS  PubMed  Google Scholar 

  144. Bohdanowicz M, Balkin DM, De Camilli P, Grinstein S (2011) Recruitment of OCRL and Inpp5B to phagosomes by Rab5 and APPL1 depletes phosphoinositides and attenuates Akt signaling. Mol Biol Cell 23(1):176–187. doi:10.1091/mbc.E11-06-0489

    Article  PubMed  CAS  Google Scholar 

  145. Lu N, Shen Q, Mahoney TR, Neukomm LJ, Wang Y, Zhou Z (2012) Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic waves of phagosomal PtdIns(3)P critical for the degradation of apoptotic cells. PLoS Biol 10(1):e1001245. doi:10.1371/journal.pbio.1001245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Cheng S, Wu Y, Lu Q, Yan J, Zhang H, Wang X (2013) Autophagy genes coordinate with the class II PI/PtdIns 3-kinase PIKI-1 to regulate apoptotic cell clearance in C. elegans. Autophagy 9(12):2022–2032. doi:10.4161/auto.26323

    Article  CAS  PubMed  Google Scholar 

  147. Huang S, Jia K, Wang Y, Zhou Z, Levine B (2012) Autophagy genes function in apoptotic cell corpse clearance during C. elegans embryonic development. Autophagy 9(2). pii: 22352

  148. Chen D, Xiao H, Zhang K, Wang B, Gao Z, Jian Y, Qi X, Sun J, Miao L, Yang C (2010) Retromer is required for apoptotic cell clearance by phagocytic receptor recycling. Science 327(5970):1261–1264. doi:10.1126/science.1184840

    Article  CAS  PubMed  Google Scholar 

  149. Kinchen JM, Doukoumetzidis K, Almendinger J, Stergiou L, Tosello-Trampont A, Sifri CD, Hengartner MO, Ravichandran KS (2008) A pathway for phagosome maturation during engulfment of apoptotic cells. Nat Cell Biol 10(5):556–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Li W, Zou W, Zhao D, Yan J, Zhu Z, Lu J, Wang X (2009) C. elegans Rab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5. Development 136(14):2445–2455

    Article  CAS  PubMed  Google Scholar 

  151. Kinchen JM, Ravichandran KS (2010) Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells. Nature 464(7289):778–782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Nieto C, Almendinger J, Gysi S, Gomez-Orte E, Kaech A, Hengartner MO, Schnabel R, Moreno S, Cabello J (2010) ccz-1 mediates the digestion of apoptotic corpses in C. elegans. J Cell Sci 123(Pt 12):2001–2007. doi:10.1242/jcs.062331

    Article  CAS  PubMed  Google Scholar 

  153. Yu X, Lu N, Zhou Z (2008) Phagocytic receptor CED-1 initiates a signaling pathway for degrading engulfed apoptotic cells. PLoS Biol 6(3):e61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Xiao H, Chen D, Fang Z, Xu J, Sun X, Song S, Liu J, Yang C (2009) Lysosome biogenesis mediated by vps-18 affects apoptotic cell degradation in Caenorhabditis elegans. Mol Biol Cell 20(1):21–32. doi:10.1091/mbc.E08-04-0441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Sasaki A, Nakae I, Nagasawa M, Hashimoto K, Abe F, Saito K, Fukuyama M, Gengyo-Ando K, Mitani S, Katada T, Kontani K (2013) Arl8/ARL-8 functions in apoptotic cell removal by mediating phagolysosome formation in Caenorhabditis elegans. Mol Biol Cell 24(10):1584–1592. doi:10.1091/mbc.E12-08-0628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Mangahas PM, Yu X, Miller KG, Zhou Z (2008) The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans. J Cell Biol 180(2):357–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Lu Q, Zhang Y, Hu T, Guo P, Li W, Wang X (2008) C. elegans Rab GTPase 2 is required for the degradation of apoptotic cells. Development 135(6):1069–1080. doi:10.1242/dev.016063

    Article  CAS  PubMed  Google Scholar 

  158. Guo P, Hu T, Zhang J, Jiang S, Wang X (2010) Sequential action of Caenorhabditis elegans Rab GTPases regulates phagolysosome formation during apoptotic cell degradation. Proc Natl Acad Sci USA 107(42):18016–18021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Xu M, Liu Y, Zhao L, Gan Q, Wang X, Yang C (2014) The lysosomal cathepsin protease CPL-1 plays a leading role in phagosomal degradation of apoptotic cells in Caenorhabditis elegans. Mol Biol Cell 25(13):2071–2083. doi:10.1091/mbc.E14-01-0015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Huang J, Wang H, Chen Y, Wang X, Zhang H (2012) Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance. Development 139(24):4613–4622. doi:10.1242/dev.086769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Chai Y, Tian D, Yang Y, Feng G, Cheng Z, Li W, Ou G (2012) Apoptotic regulators promote cytokinetic midbody degradation in C. elegans. J Cell Biol 199(7):1047–1055. doi:10.1083/jcb.201209050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We apologize to colleagues whose work could not be mentioned owing to space constraint. We thank Shiya Cheng, Qiwen Gan, and Mengli Shi for assistance in figure preparation and Dr. Isabel Hanson for editing services. Research in the authors’ laboratories was supported by the National Natural Science Foundation of China (31325015 to X.W., 31025015 and 31230043 to C.Y.), the National Basic Research Program of China (2010CB835202, 2013CB910101, and 2014CB849700 to X.W., 2013CB910102 and 2011CB910102 to C.Y.), the Chinese Academy of Sciences (KJZD-EW-L08 to C.Y.), and an International Early Career Scientist grant from the Howard Hughes Medical Institute to X.W.

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  1. National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing, 102206, China

    Xiaochen Wang

  2. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, Beijing, 100101, China

    Chonglin Yang

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Wang, X., Yang, C. Programmed cell death and clearance of cell corpses in Caenorhabditis elegans . Cell. Mol. Life Sci. 73, 2221–2236 (2016). https://doi.org/10.1007/s00018-016-2196-z

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