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Cell Host Microbe. 2010 Aug 19;8(2):137-46. doi: 10.1016/j.chom.2010.07.002. Epub 2010 Jul 30.

A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy.

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1
Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Abstract

Autophagy mediates the degradation of cytoplasmic contents in the lysosome and plays a significant role in immunity. Lipid second messengers have previously been implicated in the regulation of autophagy. Here, we demonstrate a signaling role for diacylglycerol (DAG) in antibacterial autophagy. DAG production was necessary for efficient autophagy of Salmonella, and its localization to bacteria-containing phagosomes preceded autophagy. The actions of phospholipase D and phosphatidic acid phosphatase were required for DAG generation and autophagy. Furthermore, the DAG-responsive delta isoform of protein kinase C was required, as were its downstream targets JNK and NADPH oxidase. Previous studies have revealed a role for the ubiquitin-binding adaptor molecules p62 and NDP52 in autophagy of S. Typhimurium. We observed bacteria-containing autophagosomes colocalizing individually with either DAG or ubiquitinated proteins, indicating that both signals can act independently to promote antibacterial autophagy. These findings reveal an important role for DAG-mediated PKC function in mammalian antibacterial autophagy.

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PMID:
20674539
PMCID:
PMC3668700
DOI:
10.1016/j.chom.2010.07.002
[Indexed for MEDLINE]
Free PMC Article

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