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

D. discoideum GPCR 介导的趋化机制

• 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
• 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

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.

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