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Plos Genetics : Chemical Genetics Reveals an Rgs, Volume 2

By Mango, Susan

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Book Id: WPLBN0003923307
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Genetics : Chemical Genetics Reveals an Rgs, Volume 2  
Author: Mango, Susan
Volume: Volume 2
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Publication Date:
Publisher: Plos


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Mango, S. (n.d.). Plos Genetics : Chemical Genetics Reveals an Rgs, Volume 2. Retrieved from

Description : 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-aq (G-protein alpha subunit). Our studies suggest that the small molecules act at the level of the RGS/G-aq signaling complex, and define new mutations in both RGS and G-aq, including a unique hypo-adapation allele of G-aq. These findings suggest that therapeutics targeted to downstream components of GPCR signaling may be effective for treatment of diseases involving inappropriate receptor activation.


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