The engulfment process of programmed cell death in Caenorhabditis elegans

Annual Review of Cell and Developmental Biology

Volumn 20, Issue , 2004, Pages 193-221

  Reddien, Peter W ^a   Horvitz, H Robert ^b  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Apoptosis; Migration; Phagocytosis; Rac; Signaling

Indexed keywords

ADAPTOR PROTEIN; GUANOSINE TRIPHOSPHATASE; LIPOCORTIN 1; PHOSPHATIDYLSERINE; RAC PROTEIN;

APOPTOSIS; CAENORHABDITIS ELEGANS; CELL DEATH; CELL MIGRATION; HUMAN; MACROPHAGE; MAMMAL; METAZOON; NERVE FIBER; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; CAENORHABDITIS ELEGANS; PHAGOCYTOSIS; SIGNAL TRANSDUCTION;

CAENORHABDITIS; CAENORHABDITIS ELEGANS; MAMMALIA; METAZOA; NEMATODA;

EID: 8444252166     PISSN: 10810706     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.cellbio.20.022003.114619     Document Type: Review

References (147)

1. Adams JM. 2003. Ways of dying: multiple pathways to apoptosis. Genes Dev. 17:2481-95
2. Albert ML, Kim JI, Birge RB. 2000. αvβ5 integrin recruits the CrkII-Dock180-Rac1 complex for phagocytosis of apoptotic cells. Nat. Cell Biol. 2:899-905
3. Albert ML, Pearce SF, Francisco LM, Sauter B, Roy P, et al. 1998. Immature dendritic cells phagocytose apoptotic cells via αvβ5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J. Exp. Med. 188:1359-68
4. Albina JE, Cui S, Mateo RB, Reichner JS. 1993. Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J. Immunol. 150:5080-85
5. Arur S, Uche U, Rezaul K, Fong M, Scranton V, et al. 2003. Annexin I is an endogenous ligand that mediates apoptotic engulfment. Dev. Cell 4:587-98
6. Avery L, Horvitz HR. 1987. A cell that dies during wild-type C. elegans development can function as a neuron in a ced-3 mutant. Cell 51:1071-78
7. Barnes H, Larsen B, Tyers M, van Der Geer P. 2001. Tyrosine- phosphorylated low density lipoprotein receptor-related protein 1 (Lrp1) associates with the adaptor protein SHC in SRC-transformed cells. J. Biol. Chem. 276:19119-25
8. s-induced neurodegeneration in Caenorhabditis elegans. J. Neurosci. 18:2871-80
9. Botto M, Dell'Agnola C, Bygrave AE, Thompson EM, Cook HT, et al. 1998. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat. Genet. 19:56-59
10. Bourne HR, Sanders DA, McCormick F. 1991. The GTPase superfamily: conserved structure and molecular mechanism. Nature 349:117-27
11. Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, et al. 2002. Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat. Cell Biol. 4:574-82
12. Callahan MK, Williamson P, Schlegel RA. 2000. Surface expression of phosphatidylserine on macrophages is required for phagocytosis of apoptotic thymocytes. Cell Death Differ. 7:645-53
13. Callebaut I, Mignotte V, Souchet M, Mornon JP. 2003. EMI domains are widespread and reveal the probable orthologs of the Caenorhabditis elegans CED-1 protein. Biochem. Biophys. Res. Commun. 300:619-23
14. Caron E, Hall A. 1998. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 282:1717-21
15. Chalfie M, Sulston J. 1981. Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev. Biol. 82:358-70
16. L sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell 8:705-11
17. Chimini G, Chavrier P. 2000. Function of Rho family proteins in actin dynamics during phagocytosis and engulfment. Nat. Cell Biol. 2:E191-96
18. Chung S, Gumienny TL, Hengartner MO, Driscoll M. 2000. A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans. Nat. Cell Biol. 2:931-7
19. Clissold PM, Ponting CP. 2001. JmjC: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2■. Trends Biol. Sci. 26:7-9
20. Cohen PL, Caricchio R, Abraham V, Camenisch TD, Jennette JC, et al. 2002. Delayed apoptotic cell clearance and Lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J. Exp. Med. 196:135-40
21. 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 93:519-29
22. Cui P, Baoming Q, Liu N, Pan G, Pei D. 2004. Nuclear localization of the phosphatidylserine receptor protein via multiple nuclear localization signals. Exp. Cell. Res. 293:154-63
23. Cui S, Reichner JS, Mateo RB, Albina JE. 1994. Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or -independent mechanisms. Cancer Res. 54:2462-67
24. Devitt A, Moffatt OD, Raykundalia C, Capra JD, Simmons DL, Gregory CD. 1998. Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 392:505-9
25. Diez-Roux G, Lang RA. 1997. Macrophages induce apoptosis in normal cells in vivo. Development 124:3633-38
26. Driscoll M, Chalfie M. 1991. The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration. Nature 349:588-93
27. Duffield JS. 2003. The inflammatory macrophage: a story of Jekyll and Hyde. Clin. Sci. 104:27-38
28. Ellis HM, Horvitz HR. 1986. Genetic control of programmed cell death in the nematode C. elegans. Cell 44:817-29
29. Ellis RE, Horvitz HR. 1991. Two C. elegans genes control the programmed deaths of specific cells in the pharynx. Development 112:591-603
30. Ellis RE, Jacobson DM, Horvitz HR. 1991a. Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. Genetics 129:79-94
31. Ellis RE, Yuan J, Horvitz HR. 1991b. Mechanisms and functions of cell death. Annu. Rev. Cell Biol. 7:663-98
32. Erickson M, Galletta BJ, Abmayr SM. 1997. Drosophila myoblast city encodes a conserved protein that is essential for myoblast fusion, dorsal closure, and cytoskeletal organization. J. Cell Biol. 138:589-603
33. Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM. 2000. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85-90
34. Fadok VA, de Cathelineau A, Daleke DL, Henson PM, Bratton DL. 2001. Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts. J. Biol. Chem. 276:1071-77
35. 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. 148:2207-16
36. Ferguson EL, Horvitz HR. 1985. Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans. Genetics 110:17-72
37. Ferguson EL, Sternberg PW, Horvitz HR. 1987. A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. Nature 326:259-67
38. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806-11
39. Franc NC, Dimarcq J-L, Lagueux M, Hoffmann J, Ezekowitz RAB. 1996. Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells. Immunity 4:431-43
40. Franc NC, Heitzler P, Ezekowitz RA, White K. 1999. Requirement for croquemort in phagocytosis of apoptotic cells in Drosophila. Science 284:1991-14
41. Gavrieli Y, Sherman Y, Ben-Sasson SA. 1992. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol. 119:493-501
42. Glücksmann A. 1951. Cell deaths in normal vertebrate ontogeny. Biol. Rev. 26:59-86
43. Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, et al. 2000. Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. J. Biol. Chem. 275:25616-24
44. Grimsley CM, Kinchen JM, Tosello-Trampont AC, Brugnera E, Haney LB, et al. 2004. Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. J. Biol. Chem. 279:6087-97
45. Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, et al. 2001. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 107:27-41
46. Gumienny TL, Lambie E, Hartwieg E, Horvitz HR, Hengartner MO. 1999. Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development 126:1011-22
47. Hall DH, Gu G, Garcia-Anoveros J, Gong L, Chalfie M, Driscoll M. 1997. Neuropathology of degenerative cell death in Caenorhabditis elegans. J. Neurosci. 17:1033-45
48. Hamon Y, Broccardo C, Chambenoit O, Luciani MF, Toti F, et al. 2000. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat. Cell Biol. 2:399-406
49. Hasegawa H, Kiyokawa E, Tanaka S, Nagashima K, Gotoh N, et al. 1996. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Mol. Cell Biol. 16:1770-76
50. Hedgecock EM, Sulston JE, Thomson JN. 1983. Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. Science 220:1277-79
51. Heemels MT. 2000. Apoptosis. Nature 407:769
52. Hengartner MO. 2001. Apoptosis: corralling the corpses. Cell 104:325-28
53. Hengartner MO, Horvitz HR. 1994. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell 76:665-76
54. Hermann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR. 1998. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum. 41:1241-50
55. Higgins CF. 1992. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 8:67-113
56. Hoeppner DJ, Hengartner MO, Schnabel R. 2001. Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans. Nature 412:202-6
57. Howell BW, Lanier LM, Frank R, Gertler FB, Cooper JA. 1999. The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids. Mol. Cell Biol. 19:5179-88
58. Hughes DA, Fraser IP, Gordon S. 1995. Murine macrophage scavenger receptor: in vivo expression and function as receptor for macrophage adhesion in lymphoid and non-lymphoid organs. Eur. J. Immunol. 25:466-73
59. Jacobson MD, Weil M, Raff MC. 1997. Programmed cell death in animal development. Cell 88:347-54
60. Jansen G, Hazendonk E, Thijssen KL, Plasterk RH. 1997. Reverse genetics by chemical mutagenesis in Caenorhabditis elegans. Nat. Genet. 17:119-21
61. Kaibuchi K, Kuroda S, Amano M. 1999. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Ann. Rev. Biochem. 68:459-86
62. Katoh H, Negishi M. 2003. RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature 424:461-64
63. Kavanaugh WM, Turck CW, Williams LT. 1995. PTB domain binding to signaling proteins through a sequence motif containing phosphotyrosine. Science 268:1177-79
64. Kerr JF, Wyllie AH, Currie AR. 1972. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239-57
65. Kiyokawa E, Hashimoto Y, Kurata T, Sugimura H, Matsuda M. 1998. Evidence that DOCK180 up-regulates signals from the CrkII-p130(Cas) complex. J. Biol. Chem. 273:24479-84
66. Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA. 1998. CAS/Crk coupling serves as a "molecular switch" for induction of cell migration. J. Cell Biol. 140:961-72
67. Koch CA, Anderson D, Moran MF, Ellis C, Pawson T. 1991. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 252:668-74
68. Korswagen HC, Park JH, Ohshima Y, Plasterk RH. 1997. An activating mutation in a Caenorhabditis elegans Gs protein induces neural degeneration. Genes Dev. 11:1493-503
69. Krieger M, Herz J. 1994. Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Annu. Rev. Biochem. 63:601-37
70. Lang R, Lustig M, Francois F, Sellinger M, Plesken H. 1994. Apoptosis during macrophage-dependent ocular tissue remodelling. Development 120:3395-403
71. Lang RA, Bishop JM. 1993. Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 74:453-62
72. Lauber K, Bohn E, Krober SM, Xiao YJ, Blumenthal SG, et al. 2003. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113:717-30
73. Leverrier Y, Ridley AJ. 2001. Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis by macrophages. Curr. Biol. 11:195-99
74. Li MO, Sarkisian MR, Mehal WZ, Rakic P, Flavell RA. 2003. Phosphatidylserine receptor is required for the clearance of apoptotic cells. Science 302:1560-63
75. Liu QA, Hengartner MO. 1998. Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C. elegans. Cell 93:961-72
76. Liu QA, Hengartner MO. 1999. Human CED-6 encodes a functional homologue of the Caenorhabditis elegans engulfment protein CED-6. Curr. Biol. 9:1347-50
77. Luciani MF, Chimini G. 1996. The ATP binding cassette transporter ABC1, is required for the engulfment of corpses generated by apoptotic cell death. EMBO J. 15:226-35
78. Lundquist EA, Reddien PW, Hartwieg E, Horvitz HR, Bargmann CI. 2001. Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis. Development 128:4475-88
79. 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. 1:454-56
80. Martin SJ, Reutelingsperger CPM, McGahon AJ, Rader JA, van Schie RCAA, et al. 1995. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med. 182:1545-56
81. Massol P, Montcourrier P, Guillemot JC, Chavrier P. 1998. Fc receptor-mediated phagocytosis requires CDC42 and Rac1. EMBO J. 17:6219-29
82. Matsuda M, Tanaka S, Nagata S, Kojima A, Kurata T, Shibuya M. 1992. Two species of human CRK cDNA encode proteins with distinct biological activities. Mol. Cell Biol. 12:3482-89
83. Meier P, Finch A, Evan G. 2000. Apoptosis in development. Nature 407:796-801
84. Metzstein MM, Stanfield GM, Horvitz HR. 1998. Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet. 14:410-16
85. Nagata K, Ohashi K, Nakano T, Arita H, Zong C, et al. 1996. Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J. Biol. Chem. 271:30022-27
86. Nakano T, Ishimoto Y, Kishino J, Umeda M, Inoue K, et al. 1997. Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6. J. Biol. Chem. 272:29411-14
87. Nobes CD, Hall A. 1995. Rho, rac, and cdc42 GTPases regulate the assembly of multi-molecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81:53-62
88. Ogden CA, deCathelineau A, Hoffmann PR, Bratton D, Ghebrehiwet B, et al. 2001. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J. Exp. Med. 194:781-95
89. Orso E, Broccardo C, Kaminski WE, Bottcher A, Liebisch G, et al. 2000. Transport of lipids from Golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice. Nat. Genet. 24:192-96
90. Pawson T, Scott JD. 1997. Signaling through scaffold, anchoring, and adaptor proteins. Science 278:2075-80
91. Platt N, da Silva RP, Gordon S. 1998. Recognizing death: the phagocytosis of apoptotic cells. Trends Cell Biol. 8:365-72
92. Platt N, Suzuki H, Kurihara Y, Kodama T, Gordon W. 1996. Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proc. Natl. Acad. Sci. USA 93:12456-60
93. Potter PK, Cortes-Hernandez J, Quartier P, Botto M, Walport MJ. 2003. Lupus-prone mice have an abnormal response to thioglycolate and an impaired clearance of apoptotic cells. J. Immunol. 170:3223-32
94. Pradhan D, Krahling S, Williamson P, Schlegel RA. 1997. Multiple systems for recognition of apoptotic lymphocytes by macrophages. Mol. Biol. Cell 8:767-78
95. Rabinovitch M. 1995. Professional and non-professional phagocytes: an introduction. Trends Cell Biol. 5:85-87
96. Reddien PW, Cameron S, Horvitz HR. 2001. Phagocytosis promotes programmed cell death in C. elegans. Nature 412:198-202
97. Reddien PW, Horvitz HR. 2000. CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat. Cell Biol. 2:131-36
98. Ren Y, Savill J. 1998. Apoptosis: the importance of being eaten. Cell Death Differ. 5:563-68
99. Ridley AJ, Hall A. 1992. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389-99
100. Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. 1992. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70:401-10
101. Ring GH, Lakkis FG. 1999. Breakdown of self-tolerance and the pathogenesis of autoimmunity. Semin. Nephrol. 19:25-33
102. Robertson AMG, Thomson JN. 1982. Morphology of programmed cell death in the ventral nerve cord of C. elegans larvae. J. Embryol. Exp. Morphol. 67:89-100
103. Rudin CM, Thompson CB. 1997. Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu. Rev. Med. 48:267-81
104. Ruetz S, Gros P. 1994. Phosphatidylcholine translocase: a physiological role for the mdr2 gene. Cell 77:1-20
105. Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. 2000. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J. Exp. Med. 191:423-34
106. Savill J. 1997. Apoptosis in resolution of inflammation. J. Leukoc. Biol. 61:375-80
107. Savill J, Dransfield I, Hogg N, Haslett C. 1990. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature 343:170-73
108. Savill J, Gregory C, Haslett C. 2003. Eat me or die. Science 302:1516-17
109. Savill J, Hogg N, Ren Y, Haslett C. 1992. Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J. Clin. Invest. 90:1513-22
110. Savill JS, Henson PM, Haslett C. 1989. Phagocytosis of aged human neutrophils by macrophages is mediated by a novel "charge-sensitive" recognition mechanism. J. Clin. Invest. 84:1518-27
111. Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, et al. 2001. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411:207-11
112. Shaham S. 1998. Identification of multiple Caenorhabditis elegans caspases and their potential roles in proteolytic cascades. J. Biol. Chem. 273:35109-17
113. Shaham S, Horvitz HR. 1996. Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities. Genes Dev. 10:578-91
114. Shaham S, Reddien PW, Davies B, Horvitz HR. 1999. Mutational analysis of the Caenorhabditis elegans cell-death gene ced-3. Genetics 153:1655-71
115. Shaw G. 1996. The pleckstrin homology domain: an intriguing multifunctional protein module. BioEssays 18:35-46
116. Shi Y. 2002. Mechanisms of caspase activation and inhibition during apoptosis. Mol. Cell 9:459-70
117. Smit JJM, Schinkel AH, Elferink RPJO, Groen AK, Wagenaar E, et al. 1993. Homozygous disruption of the murine mdr2 p-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75:451-62
118. Smits E, Van Criekinge W, Plaetinck G, Bogaert T. 1999. The human homologue of Caenorhabditis elegans CED-6 specifically promotes phagocytosis of apoptotic cells. Curr. Biol. 9:1351-54
119. Steven R, Kubiseski TJ, Zheng H, Kulkarni S, Mancillas J, et al. 1998. UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans. Cell 92:785-95
120. Su HP, Brugnera E, Van Criekinge W, Smits E, Hengartner M, et al. 2000. Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells. J. Biol. Chem. 275:9542-49
121. Su HP, Nakada-Tsukui K, Tosello-Trampont AC, Li Y, Bu G, et al. 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. 277:11772-79
122. Sulston JE, Horvitz HR. 1977. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev. Biol. 56:110-56
123. Sulston JE, Schierenberg E, White JG, Thomson JN. 1983. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol. 100:64-119
124. Taylor PR, Carugati A, Fadok VA, Cook HT, Andrews M, et al. 2000. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J. Exp. Med. 192:359-66
125. Thompson CB. 1995. Apoptosis in the pathogenesis and treatment of disease. Science 267:1456-62
126. Thornberry NA, Lazebnik Y. 1998. Caspases: enemies within. Science 281:1312-16
127. Tosello-Trampont AC, Brugnera E, Ravichandran KS. 2001. Evidence for a conserved role for CRKII and Rac in engulfment of apoptotic cells. J. Biol. Chem. 276:13797-802
128. Turner C, Devitt A, Parker K, MacFarlane M, Giuliano M, et al. 2003. Macrophage-mediated clearance of cells undergoing caspase-3-independent death. Cell Death Differ. 10:302-12
129. Van Aelst L, D'Souza-Schorey C. 1997. Rho GTPases and signaling networks. Genes Dev. 11:2295-322
130. van de Loosdrecht AA, Ossenkoppele GJ, Beelen RH, Broekhoven MG, Drager AM, Langenhuijsen MM. 1993. Apoptosis in tumor necrosis factor-alpha-dependent, monocyte-mediated leukemic cell death: a functional, morphologic, and flow-cytometric analysis. Exp. Hematol. 21:1628-39
131. van den Eijnde SM, Boshart L, Baehrecke EH, De Zeeuw CI, Reutlingsperger CPM, Vermeij-Keers C. 1998. Cell surface exposure of phosphatidylserine during apoptosis is phylogenetically conserved. Apoptosis 3:9-16
132. Wang X, Wu YC, Fadok V, Lee MC, Gengyo-Ando K, et al. 2003. Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Science 302:1563-66
133. White JG, Southgate E, Thomson JN. 1991. On the nature of undead cells in the nematode Caenorhabditis elegans. Philos. Trans. R. Soc. London Ser. B 331:263-71
134. Woo M, Hakem R, Soengas MS, Duncan GS, Shahinian A, et al. 1998. Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev. 12:806-19
135. Wu YC, Horvitz HR. 1998a. The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters. Cell 93:951-60
136. Wu YC, Horvitz HR. 1998b. C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 392:501-4
137. 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. 14:536-48
138. 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 1:491-502
139. Wyllie AH. 1980. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555-56
140. Wyllie AH, Kerr JFR, Currie AR. 1980. Cell death: the significance of apoptosis. Int. Rev. Cytol. 68:251-306
141. Yajnik V, Paulding C, Sordella R, McClatchey AI, Saito M, et al. 2003. DOCK4, a GTPase activator, is disrupted during tumorigenesis. Cell 112:673-84
142. 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 116:309-20
143. 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 75:641-52
144. Zhou Z, Caron E, Hartwieg E, Hall A, Horvitz HR. 2001a. The C. elegans PH domain protein CED-12 regulates cytoskeletal reorganization via a Rho/Rac GTPase signaling pathway. Dev. Cell 1:477-89
145. Zhou Z, Hartwieg E, Horvitz HR. 2001b. CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 104:43-56
146. Zipkin ID, Kindt RM, Kenyon CJ. 1997. Role of a new Rho family member in cell migration and axon guidance in C. elegans. Cell 90:883-94
147. 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 90:405-13