title: GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin A, localizes to the Golgi and is cleaved by furin.
abstract: A number of toxins, including exotoxin A (PE) of Pseudomonas aeruginosa, kill cells by inhibiting protein synthesis. PE kills by ADP-ribosylation of the translation elongation factor 2, but many of the host factors required for entry, membrane translocation, and intracellular transport remain to be elucidated. A genome-wide genetic screen in human KBM7 cells was performed to uncover host factors used by PE, several of which were confirmed by CRISPR/Cas9-gene editing in a different cell type. Several proteins not previously implicated in the PE intoxication pathway were identified, including GPR107, an orphan G-protein-coupled receptor. GPR107 localizes to the trans-Golgi network and is essential for retrograde transport. It is cleaved by the endoprotease furin, and a disulfide bond connects the two cleaved fragments. Compromising this association affects the function of GPR107. The N-terminal region of GPR107 is critical for its biological function. GPR107 might be one of the long-sought receptors that associates with G-proteins to regulate intracellular vesicular transport.
authors.affiliation: From the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142.
authors.forename: Fikadu G
authors.initials: FG
authors.lastname: Tafesse
authors.affiliation: From the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142.
authors.forename: Carla P
authors.initials: CP
authors.lastname: Guimaraes
authors.affiliation: From the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: the Stanford School of Medicine, Stanford, California 94305.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Carette
authors.affiliation: the Harvard Medical School, Boston, Massachusetts 02115, and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lory
authors.affiliation: the Netherlands Cancer Institute, Postbus 90203, 1006 BE Amsterdam, The Netherlands.
authors.forename: Thijn R
authors.initials: TR
authors.lastname: Brummelkamp
authors.affiliation: From the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, ploegh@wi.mit.edu.
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000633:toxicity*; D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D001483:Base Sequence; D017931:DNA Primers; D004705:Endocytosis; D005098:Exotoxins / Q000235:genetics / Q000633:toxicity*; D045683:Furin / Q000378:metabolism*; D009154:Mutation; D016133:Polymerase Chain Reaction; D021381:Protein Transport; D059748:Proteolysis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism* / Q000502:physiology; D037521:Virulence Factors / Q000235:genetics / Q000633:toxicity*; D021601:trans-Golgi Network / Q000378:metabolism*; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D017931:DNA Primers; D005098:Exotoxins; D045683:Furin; D043562:Receptors, G-Protein-Coupled; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C521099:GPR107 protein, human
keywords: Bacterial Toxin; Furin; G-protein-coupled Receptor (GPCR); GPR107; Haploid Genetic Screen; Intracellular Trafficking; KBM7; Pseudomonas aeruginosa Exotoxin A; Sortase A