A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy.
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.
Shahnazari
Shahab
S
Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Yen
Wei-Lien
WL
Birmingham
Cheryl L
CL
Shiu
Jessica
J
Namolovan
Anton
A
Zheng
Yiyu T
YT
Nakayama
Keiko
K
Klionsky
Daniel J
DJ
Brumell
John H
JH
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D004075:Diglycerides / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D010711:Phosphatidate Phosphatase / Q000502:physiology; D010739:Phospholipase D / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000502:physiology*; D015398:Signal Transduction
D004075:Diglycerides; D011493:Protein Kinase C; D010711:Phosphatidate Phosphatase; D010739:Phospholipase D