GPR107, a GPCR Essential for Intoxication by P. aeruginosa Exotoxin A, Localizes to the Golgi and is Cleaved by Furin [Microbiology]

July 16th, 2014 by Tafesse, F. G., Guimaraes, C. P., Maruyama, T., Carette, J. E., Lory, S., Brummelkamp, T. R., Ploegh, H. L.

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 GPCR. 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.