“RGS-ome” siRNA screen published



We performed medium-throughput calcium mobilization assays of agonist-stimulated muscarinic acetylcholine and protease-activated receptors in HEK293 cells transfected with individual members of a “pooled duplex” siRNA library targeting all conventional human RGS transcripts. Only knockdown of RGS11 increased both carbachol-mediated calcium mobilization and inositol phosphate accumulation. Surprisingly, we found that knockdown of RGS8 and RGS9, but not other conventional RGS proteins, significantly decreased carbachol-mediated calcium mobilization, while only RGS8 knockdown decreased PAR-1-mediated calcium mobilization. Our data suggest a cellular role for RGS8 in the stable surface expression of M3 mAChR and PAR-1, as well as a specific and opposing set of functions for RGS9 and RGS11 in modulating carbachol responsiveness similar to that seen in C. elegans. See PMID: 20573995

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