The mechanisms underlying the GPCR-mediated chemotaxis in D. discoideum

专业吞噬细胞盘状芽孢杆菌如何追逐和识别各种细菌作为食物--一种新的MAMP受体的发现 盘状变形虫是一种专业的吞噬细胞，它通过趋化作用捕捉细菌，并通过吞噬作用将它们吞噬为食物。虽然早在40多年前就有研究表明，细菌释放的叶酸是盘状芽孢杆菌寻找细菌的化学诱导剂，但至今还没有鉴定出叶酸受体。使用定量磷蛋白质组学技术，我们发现孤儿GPCRfAR1介导对叶酸的趋化作用以追逐细菌，并在革兰氏细菌的吞噬过程中发挥作用(潘等人。Dev Cell，2016)。我们发现FAR1同时识别化学诱导剂叶酸和吞噬线索脂多糖(LPS)，这是细菌表面的主要成分。我们的计算模拟和实验相结合表明，与趋化相关的反应也可以促进包裹着化学吸引剂的颗粒的吞噬。最后，FAR1的胞外Venus-Flytrap结构域是叶酸和脂多糖的结合部位。因此，fAR1代表了模式识别受体的一个新成员，并介导来自细菌表面和扩散趋化剂的信号，以重组肌动蛋白进行趋化和吞噬(Panet al PLOS Biology，2018)。我们正在努力识别革兰氏细菌其他表面分子的受体。

How professional phagocytes, D. discoideum, chase and recognize various bacteria as food-The discovery of a new MAMP receptor The social amoeba D. discoideum is a professional phagocyte that catches bacteria via chemotaxis and engulf them as food via phagocytosis. Although folic acid released by bacteria was shown to be the chemoattractant for D. discoideum to seek bacteria more than 40 years ago, a folic acid receptor had not been identified. Using a quantitative phosphor-proteomic technique, we find that an orphan GPCR, fAR1, mediates chemotaxis toward folate to chase bacteria and plays a role in the phagocytosis of Gram- bacteria (Pan et al. Dev Cell, 2016). We show that fAR1 simultaneously recognizes the chemoattractant folate and the phagocytic cue lipopolysaccharide (LPS), a major component of bacterial surfaces. Our computational simulations combined with experiments show that responses associated with chemotaxis can also promote engulfment of particles coated with chemoattractants. Finally, the extracellular Venus-Flytrap domain of fAR1 acts as the binding site for both folate and lipopolysaccharide. Thus, fAR1 represents a new member of the pattern recognition receptors and mediates signaling from both bacterial surfaces and diffusible chemoattractants to reorganize actin for chemotaxis and phagocytosis (Pan et al PLOS Biology, 2018). We are trying to identify receptors for other surface molecules of Gram+ bacteria.