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

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Listed:
  • Jason M. Kinchen

    (State University of New York
    University of Zurich
    University of Virginia)

  • Juan Cabello

    (Institut für Genetik, TU Braunschweig)

  • Doris Klingele

    (University of Zurich)

  • Kelvin Wong

    (University of Zurich)

  • Richard Feichtinger

    (Xybermind GmbH)

  • Heinke Schnabel

    (Max Planck Institut für Neurobiologie)

  • Ralf Schnabel

    (Institut für Genetik, TU Braunschweig)

  • Michael O. Hengartner

    (University of Zurich)

Abstract

The removal of apoptotic cells is essential for the physiological well being of the organism1,2,3. In Caenorhabditis elegans, two conserved, partially redundant genetic pathways regulate this process4,5,6. 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)7,8. In the second group, the candidate receptor CED-1 (CD91/LRP/SREC) probably recognizes an unknown ligand on the apoptotic cell9 and signals via its cytoplasmic tail to the adaptor protein CED-6 (hCED-6/GULP)10,11, whereas CED-7 (ABCA1) is thought to play a role in membrane dynamics12. 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.

Suggested Citation

  • Jason M. Kinchen & Juan Cabello & Doris Klingele & Kelvin Wong & Richard Feichtinger & Heinke Schnabel & Ralf Schnabel & Michael O. Hengartner, 2005. "Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans," Nature, Nature, vol. 434(7029), pages 93-99, March.
    • Handle: RePEc:nat:nature:v:434:y:2005:i:7029:d:10.1038_nature03263
    DOI: 10.1038/nature03263
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