Guanylate-Binding Protein 1 Regulates Infection-Induced Autophagy through TBK1 Phosphorylation

IF 2.6 2区 生物学 Q3 CELL BIOLOGY
Miyako Hikichi, Hirotaka Toh, Atsuko Minowa‐Nozawa, T. Nozawa, I. Nakagawa
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引用次数: 1

Abstract

Invading bacteria can be degraded by selective autophagy, known as xenophagy. Recent studies have shown that the recruitment of autophagy adaptor proteins such as p62 to bacteria and its regulation by activated TANK-binding kinase 1 (TBK1) are required to overcome bacterial infection. However, the detailed molecular mechanisms behind this are not yet fully understood. Here, we show that the human guanylate-binding protein (GBP) family, especially GBP1, directs xenophagy against invading Group A Streptococcus (GAS) by promoting TBK1 phosphorylation. GBP1 exhibits a GAS-surrounding localization response to bacterially caused membrane damage mediated by the membrane damage sensor galectin-3. We found that GBP1 knockout attenuated TBK1 activation, followed by reduced p62 recruitment and lower bactericidal activity by xenophagy. Furthermore, GBP1-TBK1 interaction was detected by immunoprecipitation. Our findings collectively indicate that GBP1 contributes to GAS-targeted autophagy initiated by membrane damage detection by galectin-3 via TBK1 phosphorylation.
鸟苷结合蛋白1通过TBK1磷酸化调控感染诱导的自噬
入侵细菌可以通过选择性自噬来降解,称为异种自噬。最近的研究表明,细菌需要自噬适配蛋白(如p62)的募集,并通过活化的tank结合激酶1 (TBK1)对其进行调节,以克服细菌感染。然而,这背后的详细分子机制尚不完全清楚。在这里,我们发现人鸟苷结合蛋白(GBP)家族,特别是GBP1,通过促进TBK1磷酸化来指导对入侵的A群链球菌(GAS)的异食。GBP1对由膜损伤传感器半凝集素-3介导的细菌引起的膜损伤表现出气体周围的定位反应。我们发现GBP1敲除会减弱TBK1的激活,随后会减少p62的募集,并通过异种噬菌降低杀菌活性。此外,通过免疫沉淀检测GBP1-TBK1相互作用。我们的研究结果共同表明,GBP1有助于通过TBK1磷酸化半乳糖凝集素-3检测膜损伤而引发的gas靶向自噬。
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来源期刊
Cellular Microbiology
Cellular Microbiology 生物-微生物学
CiteScore
9.70
自引率
0.00%
发文量
26
审稿时长
3 months
期刊介绍: Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.
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