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PMID: 23108454 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Autophagy genes function in apoptotic cell corpse clearance during C. elegans embryonic development.

Autophagy ·Vol. 9 ·No. 2 ·2013-02-01 ·Pages 138-49

Huang S, Jia K, Wang Y, Zhou Z, Levine B

Abstract

Efficient apoptotic corpse clearance is essential for metazoan development and adult tissue homeostasis. Several autophagy proteins have been previously shown to function in apoptotic cell clearance; however, it remains unknown whether autophagy genes are essential for efficient apoptotic corpse clearance in the developing embryo. Here we show that, in Caenorhabditis elegans embryos, loss-of-function mutations in several autophagy genes that act at distinct steps in the autophagy pathway resulted in increased numbers of cell corpses and delayed cell corpse clearance. Further analysis of embryos with a null mutation in bec- 1, the C. elegans ortholog of yeast VPS30/ATG6/mammalian beclin 1 (BECN1), revealed normal phosphatidylserine exposure on dying cells. Moreover, the corpse clearance defects of bec- 1(ok691) embryos were rescued by BEC-1 expression in engulfing cells, and bec- 1(ok691) enhanced corpse clearance defects in nematodes with simultaneous mutations in the engulfment genes, ced- 1, ced- 6 or ced- 12. Together, these data demonstrate that autophagy proteins play an important role in cell corpse clearance during nematode embryonic development, and likely function in parallel to known pathways involved in corpse removal.

Keywords
C. elegans apoptotic corpse clearance autophagy cell death embryogenesis
MeSH Terms
Animals Apoptosis/genetics Autophagy/genetics Caenorhabditis elegans/cytology,embryology,genetics Caenorhabditis elegans Proteins/genetics,metabolism Cell Count Embryo, Nonmammalian/cytology,embryology,metabolism Embryonic Development/genetics Genes, Helminth/genetics Mutation/genetics Phagocytosis/genetics Phosphatidylserines/metabolism Promoter Regions, Genetic/genetics
Chemicals
Caenorhabditis elegans Proteins Phosphatidylserines
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Huang Shuyi
Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jia Kailiang
Wang Ying
Zhou Zheng
Levine Beth
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Article Info
Journal
Autophagy
Abbr.
Autophagy
ISSN
1554-8635
DOI
10.4161/auto.22352
Published
2013-02-01
Epub
2012-00-29
Pages
138-49
Language
English
Region
United States
NLM ID
101265188
PMCID
PMC3552879
Subset
IM
Grants
NCI NIH HHS · R01 CA109618 · United States
NIGMS NIH HHS · R01 GM067848 · United States
NIGMS NIH HHS · GM067848 · United States
External Links
PubMed source DOI: 10.4161/auto.22352 PMC Full Text View journal details
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