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Activation of autophagy during cell death requires the engulfment receptor Draper

Nature volume 465, pages 1093–1096 (2010)Cite this article

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Abstract

Autophagy degrades cytoplasmic components that are required for cell survival in response to starvation1. Autophagy has also been associated with cell death, but it is unclear how this is distinguished from autophagy during cell survival. Drosophila salivary glands undergo programmed cell death that requires autophagy genes2, and engulfment of salivary gland cells by phagocytes does not appear to occur3. Here we show that Draper (Drpr), the Drosophila melanogaster orthologue of the Caenorhabditis elegans engulfment receptor CED-1, is required for autophagy during cell death. Null mutations in, and salivary gland-specific knockdown of, drpr inhibit salivary gland degradation. Knockdown of drpr prevents the induction of autophagy in dying salivary glands, and expression of the Atg1 autophagy regulator in drpr mutants suppresses the failure in degradation of salivary glands. Surprisingly, drpr is required in the same dying salivary gland cells in which it regulates autophagy induction, but drpr knockdown does not prevent starvation-induced autophagy in the fat body, which is associated with survival. In addition, components of the conserved engulfment pathway are required for clearance of dying salivary glands. To our knowledge, this is the first example of an engulfment factor that is required for self-clearance of cells. Further, Drpr is the first factor that distinguishes autophagy that is associated with cell death from autophagy associated with cell survival.

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Figure 1: Draper is required for salivary gland cell degradation.
Figure 2: Draper functions downstream or in parallel to caspases during salivary gland cell death.
Figure 3: Draper is required for the induction of autophagy in dying salivary gland cells.
Figure 4: Drpr is cell-autonomously required for autophagy in dying salivary glands, but not in response to starvation in the fat body.

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Acknowledgements

We thank A. Bergmann, U. Gaul, H. Kramer, E. Kurant, T. P. Neufeld, T. E. Rusten, H. Stenmark, the Bloomington Stock Center, the VDRC, and the Developmental Studies Hybridoma Bank for flies and antibodies, and R. Simin, T. Fortier and A. Sheehan for technical support. This work was supported by American Cancer Society Postdoctoral Fellowship PF-07-258-01-CSM to MAL, NIH grants NS053538 to M.R.F. and GM079431 to E.H.B., and Merck and Co. Inc. for E.H.B. E.H.B. is a member of the UMass DERC (DK32520).

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Authors and Affiliations

  1. Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA,

    Christina K. McPhee & Eric H. Baehrecke

  2. Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA,

    Christina K. McPhee

  3. Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA,

    Mary A. Logan & Marc R. Freeman

  4. Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA,

    Marc R. Freeman

Authors
  1. Christina K. McPhee
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  2. Mary A. Logan
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  3. Marc R. Freeman
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  4. Eric H. Baehrecke
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Contributions

All the experiments were performed by C.K.M., and were designed by C.K.M and E.H.B. M.L. and M.R.F. provided critical DNA constructs and transgenic flies. All authors wrote and discussed the manuscript.

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Correspondence to Eric H. Baehrecke.

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The authors declare no competing financial interests.

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McPhee, C., Logan, M., Freeman, M. et al. Activation of autophagy during cell death requires the engulfment receptor Draper. Nature 465, 1093–1096 (2010). https://doi.org/10.1038/nature09127

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