The mechanisms underlying the GPCR-mediated chemotaxis in D. discoideum
The mechanisms underlying the GPCR-mediated chemotaxis in D. discoideum
批准号:
10272094
负责人:
Tian Jin
金额:
$88.62万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
ActinsAmoeba genusBacteriaBinding SitesBiochemicalBiological ModelsBiologyCellsChemotactic FactorsChemotaxisComplementComplexComputer AssistedComputer SimulationConsumptionCoupledCuesCyclic AMPCyclic AMP ReceptorsDetectionDictyostelium discoideumDiffuseEukaryotic CellExposure toFolic AcidFoodG-Protein-Coupled ReceptorsGenomeGoalsHeterotrimeric GTP-Binding ProteinsImmunityImmunoglobulinsInvadedInvertebratesLifeLipopolysaccharidesMediatingModelingMolecularOrganismOrphanOrthologous GenePatternPattern recognition receptorPhagocytesPhagocytosisPlayProteomicsRoleSignal PathwaySignal TransductionSurfaceTechniquesToll-like receptorsVenus FlytrapVertebratesbasecell motilityexperimental studyextracellularfluorescence imagingfolate-binding proteinimaging modalitymembermicrobialparticlepathogenpathogenic bacteriareceptorreceptor-mediated signalingresponsesocial
中文摘要
专业的吞噬细胞盘状芽孢杆菌是如何追逐和识别各种细菌作为食物的
英文摘要
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.
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