GPR107, a G-protein-coupled Receptor Essential for Intoxication by Pseudomonas aeruginosa Exotoxin A, Localizes to the Golgi and Is Cleaved by Furin

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 2014-08, Vol.289 (35), p.24005-24018
Main Authors: Tafesse, Fikadu G., Guimaraes, Carla P., Maruyama, Takeshi, Carette, Jan E., Lory, Stephen, Brummelkamp, Thijn R., Ploegh, Hidde L.
Format: Article
Language:English
Subjects:
ADP Ribose Transferases - genetics
ADP Ribose Transferases - toxicity
Bacterial Toxins - genetics
Bacterial Toxins - toxicity
Base Sequence
Cell Biology
DNA Primers
Endocytosis
Exotoxins - genetics
Exotoxins - toxicity
Furin - metabolism
Mutation
Polymerase Chain Reaction
Protein Transport
Proteolysis
Pseudomonas aeruginosa Exotoxin A
Receptors, G-Protein-Coupled - metabolism
Receptors, G-Protein-Coupled - physiology
trans-Golgi Network - metabolism
Virulence Factors - genetics
Virulence Factors - toxicity
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M114.589275