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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18
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2019
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Schwebs, David J; Pan, Miao; Adhikari, Nirakar et al. (2018) Dictyostelium Erk2 is an atypical MAPK required for chemotaxis. Cell Signal 46:154-165
Pan, Miao; Neilson, Matthew P; Grunfeld, Alexander M et al. (2018) A G-protein-coupled chemoattractant receptor recognizes lipopolysaccharide for bacterial phagocytosis. PLoS Biol 16:e2005754
Gera, Nidhi; Swanson, Kenneth D; Jin, Tian (2017) ?-Arrestin 1-dependent regulation of Rap2 is required for fMLP-stimulated chemotaxis in neutrophil-like HL-60 cells. J Leukoc Biol 101:239-251
Xu, Xuehua; Wen, Xi; Veltman, Douwe M et al. (2017) GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis. Proc Natl Acad Sci U S A 114:E10092-E10101
Xu, Xuehua; Jin, Tian (2017) ELMO proteins transduce G protein-coupled receptor signal to control reorganization of actin cytoskeleton in chemotaxis of eukaryotic cells. Small GTPases :1-9
Wen, Xi; Jin, Tian; Xu, Xuehua (2016) Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells. J Vis Exp :
Wang, Gang; Cao, Luyang; Liu, Xiaowen et al. (2016) Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation. Dev Cell 38:453-62
Pan, Miao; Xu, Xuehua; Chen, Yong et al. (2016) Identification of a Chemoattractant G-Protein-Coupled Receptor for Folic Acid that Controls Both Chemotaxis and Phagocytosis. Dev Cell 36:428-39
Cao, Xiumei; Yan, Jianshe; Shu, Shi et al. (2014) Arrestins function in cAR1 GPCR-mediated signaling and cAR1 internalization in the development of Dictyostelium discoideum. Mol Biol Cell 25:3210-21
Jin, Tian (2013) Gradient sensing during chemotaxis. Curr Opin Cell Biol 25:532-7

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