A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy.
A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy.
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DOI：
10.1016/j.chom.2010.07.002
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发表时间：
2010-08-19
影响因子：
30.3
通讯作者：
Brumell JH
中科院分区：
文献类型：
--
作者：
Shahnazari S;Yen WL;Birmingham CL;Shiu J;Namolovan A;Zheng YT;Nakayama K;Klionsky DJ;Brumell JH
自噬介导溶酶体中细胞质内容物的降解，并在先天性和适应性免疫应答中起重要作用。脂质第二信使与自噬的调节有关，但所涉及的脂质的性质及其作用机制尚未被表征。在这里，我们证明了一个新的信号作用，二酰基甘油（DAG）在抗菌自噬。DAG的产生是沙门氏菌有效自噬所必需的，并且其在自噬之前定位于含细菌的吞噬体。先前的研究揭示了泛素结合衔接分子p62和NDP 52在S.鼠伤寒。我们观察到含有细菌的自噬体与DAG或泛素化蛋白单独共定位，表明这两种信号可以独立地起作用以促进抗细菌自噬。我们确定磷脂酶D（PLD）和磷脂酸磷酸酶（PAP）的作用是DAG产生和自噬所必需的。抗细菌自噬需要蛋白激酶C的DAG响应性δ同种型，其下游靶标JNK和NADPH氧化酶也是如此。Pkc1是酵母中唯一的PKC亚型，在饥饿诱导的酿酒酵母自噬过程中发挥重要作用。这些发现揭示了DAG介导的PKC功能在哺乳动物抗细菌自噬中的重要作用，并表明PKC在真核生物自噬调节中的保守作用。
Autophagy mediates the degradation of cytoplasmic contents in the lysosome and plays a significant role in innate and adaptive immune responses. Lipid second messengers are implicated in the regulation of autophagy but the nature of the lipids involved and their mechanisms of action have yet to be characterized. Here we demonstrate a novel 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. 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 anti-bacterial autophagy. We determined that the actions of phospholipase D (PLD) and phosphatidic acid phosphatase (PAP) were required for DAG generation and autophagy. The DAG-responsive δ isoform of protein kinase C was required for anti-bacterial autophagy, as were its downstream targets JNK and NADPH oxidase. Pkc1, the single PKC isoform in yeast, was essential for starvation-induced autophagy in Saccharomyces cerevisiae. These findings reveal an important role for DAG-mediated PKC function in mammalian anti-bacterial autophagy, and suggest a conserved role for PKC in autophagy regulation in eukaryotes.
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DOI：
10.1083/jcb.152.3.519
发表时间：
2001-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kihara A;Noda T;Ishihara N;Ohsumi Y
通讯作者：
Ohsumi Y
影响因子：
2.9
作者：
Fontayne, A;Dang, PMC;El Benna, J
通讯作者：
El Benna, J
影响因子：
4.8
作者：
Denmat-Ouisse, LA;Phebidias, C;Raymond, MN
通讯作者：
Raymond, MN
DOI：
10.1006/bbrc.1994.1199
发表时间：
1994-02-28
影响因子：
3.1
作者：
GSCHWENDT, M;MULLER, HJ;MARKS, F
通讯作者：
MARKS, F
影响因子：
13.3
作者：
Kobayashi, Shouhei;Kojidani, Tomoko;Haraguchi, Tokuko
通讯作者：
Haraguchi, Tokuko