Guanylate-Binding Protein 1 Regulates Infection-Induced Autophagy through TBK1 Phosphorylation
Guanylate-Binding Protein 1 Regulates Infection-Induced Autophagy through TBK1 Phosphorylation
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DOI：
10.1155/2022/8612113
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发表时间：
2022-05
影响因子：
3.4
通讯作者：
Miyako Hikichi;Hirotaka Toh;Atsuko Minowa‐Nozawa;T. Nozawa;I. Nakagawa
中科院分区：
文献类型：
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作者：
Miyako Hikichi;Hirotaka Toh;Atsuko Minowa‐Nozawa;T. Nozawa;I. Nakagawa
入侵的细菌可以通过选择性自噬来降解，也就是所谓的异种吞噬。最近的研究表明，克服细菌感染需要p62等自噬适配蛋白的募集和激活的坦克结合蛋白1(TBK1)的调节。然而，这背后的详细分子机制还没有完全弄清楚。在这里，我们展示了人类鸟氨酸结合蛋白(GBP)家族，特别是GBP1，通过促进TBK1的磷酸化来引导异噬作用对抗入侵的A组链球菌(GAS)。GBP1对由膜损伤传感器Galectin-3介导的细菌引起的膜损伤表现出围绕气体的定位反应。我们发现，GBP1基因敲除减弱了TBK1的激活，随后减少了p62的募集，并通过异源吞噬降低了杀菌活性。免疫沉淀法检测GBP1-TBK1的相互作用。我们的发现共同表明，GBP1参与了由Galectin-3通过TBK1磷酸化检测膜损伤而启动的气体靶向自噬。
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.