GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin a, localizes to the Golgi and is cleaved by furin

Fikadu G. Tafesse, Carla P. Guimaraes, Takeshi Maruyama, Jan E. Carette, Stephen Lory, Thijn R. Brummelkamp, Hidde L. Ploegh

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)24005-24018
Number of pages14
JournalJournal of Biological Chemistry
Volume289
Issue number35
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

Furin
Exotoxins
G-Protein-Coupled Receptors
Pseudomonas aeruginosa
Clustered Regularly Interspaced Short Palindromic Repeats
Genes
Peptide Elongation Factor 2
GTP-Binding Proteins
Disulfides
Adenosine Diphosphate
trans-Golgi Network
Intracellular Membranes
Proteins
Association reactions
Membranes
Genome

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin a, localizes to the Golgi and is cleaved by furin. / Tafesse, Fikadu G.; Guimaraes, Carla P.; Maruyama, Takeshi; Carette, Jan E.; Lory, Stephen; Brummelkamp, Thijn R.; Ploegh, Hidde L.

In: Journal of Biological Chemistry, Vol. 289, No. 35, 01.01.2014, p. 24005-24018.

Research output: Contribution to journalArticle

Tafesse, Fikadu G. ; Guimaraes, Carla P. ; Maruyama, Takeshi ; Carette, Jan E. ; Lory, Stephen ; Brummelkamp, Thijn R. ; Ploegh, Hidde L. / GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin a, localizes to the Golgi and is cleaved by furin. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 35. pp. 24005-24018.
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