title: Identification of a Chemoattractant G-Protein-Coupled Receptor for Folic Acid that Controls Both Chemotaxis and Phagocytosis.
abstract: Eukaryotic phagocytes search and destroy invading microorganisms via chemotaxis and phagocytosis. The social amoeba Dictyostelium discoideum is a professional phagocyte that chases bacteria through chemotaxis and engulfs them as food via phagocytosis. G-protein-coupled receptors (GPCRs) are known for detecting chemoattractants and directing cell migration, but their roles in phagocytosis are not clear. Here, we developed a quantitative phosphoproteomic technique to discover signaling components. Using this approach, we discovered the long sought after folic acid receptor, fAR1, in D. discoideum. We showed that the seven-transmembrane receptor fAR1 is required for folic acid-mediated signaling events. Significantly, we discovered that fAR1 is essential for both chemotaxis and phagocytosis of bacteria, thereby representing a chemoattractant GPCR that mediates not only chasing but also ingesting bacteria. We revealed that a phagocyte is able to internalize particles via a chemoattractant-mediated engulfment process. We propose that mammalian phagocytes may also use this mechanism to engulf and ingest bacterial pathogens.
authors.affiliation: Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, NIH, Rockville, MD 20852, USA. Electronic address: miao.pan@nih.gov.
authors.forename: Miao
authors.initials: M
authors.lastname: Pan
authors.affiliation: Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, NIH, Rockville, MD 20852, USA.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Xu
authors.affiliation: Proteomics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, NIH, Rockville, MD 20852, USA. Electronic address: tjin@niaid.nih.gov.
authors.forename: Tian
authors.initials: T
authors.lastname: Jin
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002630:Chemotactic Factors; D043562:Receptors, G-Protein-Coupled; D005492:Folic Acid; D000242:Cyclic AMP; D000445:Aldehyde Oxidoreductases