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

D. discoideum GPCR 介导的趋化机制

基本信息

批准号：
10272094
负责人：
Tian Jin
金额：
$ 88.62万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10272094
关键词：
Actins Amoeba genus Bacteria Binding Sites Biochemical Biological Models Biology Cells Chemotactic Factors Chemotaxis Complement Complex Computer Assisted Computer Simulation Consumption Coupled Cues Cyclic AMP Cyclic AMP Receptors Detection Dictyostelium discoideum Diffuse Eukaryotic Cell Exposure to Folic Acid Food G-Protein-Coupled Receptors Genome Goals Heterotrimeric GTP-Binding Proteins Immunity Immunoglobulins Invaded Invertebrates Life Lipopolysaccharides Mediating Modeling Molecular Organism Orphan Orthologous Gene Pattern Pattern recognition receptor Phagocytes Phagocytosis Play Proteomics Role Signal Pathway Signal Transduction Surface Techniques Toll-like receptors Venus Flytrap Vertebrates base cell motility experimental study extracellular fluorescence imaging folate-binding protein imaging modality member microbial particle pathogen pathogenic bacteria receptor receptor-mediated signaling response social

项目摘要

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.

专业的吞噬细胞，D。D。迪斯科，追逐和识别各种细菌作为食物 - 发现新的MAMP受体社交变形虫D. Discoideum是一种专业的吞噬细胞，可通过趋化性吸收细菌，并通过吞噬作用将其吞噬为食物。尽管细菌释放的叶酸被证明是D. discoideum在40年前寻求细菌的趋化剂，但尚未鉴定出叶酸受体。使用定量的磷蛋白蛋白技术，我们发现孤儿GPCR FAR1介导趋化叶酸趋化以追逐细菌，并在革兰细菌的吞噬作用中起作用（Pan等人Dev Cell，2016）。我们表明，FAR1同时识别趋化叶酸和吞噬提示脂多糖（LPS），这是细菌表面的主要组成部分。我们的计算模拟与实验相结合，表明与趋化性相关的响应也可以促进与化学吸引剂覆盖的颗粒吞没。最后，FAR1的细胞外金星 - 芬斯 - 芬斯 - 芬斯 - 芬斯 - 芬斯 - 粉状结构域是叶酸和脂多糖的结合位点。因此，FAR1代表了模式识别受体的新成员，并介导了来自细菌表面和可扩散趋化剂的信号传导，以重组肌动蛋白进行趋化性和吞噬作用（Pan et al Plos Biology，2018）。我们正在尝试鉴定革兰氏+细菌其他表面分子的受体。