Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans

• Published in: Nature 2005-03, Vol.434 (7029), p.93-99
• Main Authors: Schnabel, Heinke, Feichtinger, Richard, Wong, Kelvin, Hengartner, Michael O, Kinchen, Jason M, Schnabel, Ralf, Cabello, Juan, Klingele, Doris
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Ageing, cell death; Animals; Apoptosis - physiology; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological and medical sciences; Caenorhabditis elegans; Caenorhabditis elegans - cytology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell physiology; Cellular biology; Cytoskeleton - chemistry; Cytoskeleton - metabolism; Disorders of Sex Development; Fundamental and applied biological sciences. Psychology; Genotype; Humanities and Social Sciences; letter; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular and cellular biology; multidisciplinary; Mutation; Phagocytosis - physiology; Phosphoproteins - genetics; Phosphoproteins - metabolism; Proteins; rac GTP-Binding Proteins - genetics; rac GTP-Binding Proteins - metabolism; Science; Science (multidisciplinary); Signal Transduction; Worms
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature03263

The removal of apoptotic cells is essential for the physiological well being of the organism. In Caenorhabditis elegans, two conserved, partially redundant genetic pathways regulate this process. In the first pathway, the proteins CED-2, CED-5 and CED-12 (mammalian homologues CrkII, Dock180 and ELMO, respectively) function to activate CED-10 (Rac1). In the second group, the candidate receptor CED-1 (CD91/LRP/SREC) probably recognizes an unknown ligand on the apoptotic cell and signals via its cytoplasmic tail to the adaptor protein CED-6 (hCED-6/GULP), whereas CED-7 (ABCA1) is thought to play a role in membrane dynamics. Molecular understanding of how the second pathway promotes engulfment of the apoptotic cell is lacking. Here, we show that CED-1, CED-6 and CED-7 are required for actin reorganization around the apoptotic cell corpse, and that CED-1 and CED-6 colocalize with each other and with actin around the dead cell. Furthermore, we find that the CED-10(Rac) GTPase acts genetically downstream of these proteins to mediate corpse removal, functionally linking the two engulfment pathways and identifying the CED-1, -6 and -7 signalling module as upstream regulators of Rac activation.