Chemical genetics reveals an RGS/G-protein role in the action of a compound
Chemical genetics reveals an RGS/G-protein role in the action of a compound
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DOI：
10.1371/journal.pgen.0020057
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发表时间：
2006-04-01
期刊：
影响因子：
4.5
通讯作者：
Kindt, Rachel M.
中科院分区：
文献类型：
--
作者：
Fitzgerald, Kevin;Tertyshnikova, Svetlana;Kindt, Rachel M.
We report here on a chemical genetic screen designed to address the mechanism of action of a small molecule. Small molecules that were active in models of urinary incontinence were tested on the nematode Caenorhabditis elegans, and the resulting phenotypes were used as readouts in a genetic screen to identify possible molecular targets. The mutations giving resistance to compound were found to affect members of the RGS protein/G-protein complex. Studies in mammalian systems confirmed that the small molecules inhibit muscarinic G- protein coupled receptor (GPCR) signaling involving G-alpha q (G- protein alpha subunit). Our studies suggest that the small molecules act at the level of the RGS/G-alpha q signaling complex, and define new mutations in both RGS and G-alpha q, including a unique hypo-adapation allele of G-alpha q. These findings suggest that therapeutics targeted to downstream components of GPCR signaling may be effective for treatment of diseases involving inappropriate receptor activation.
