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Modulation of receptor dynamics by the regulator of G protein signaling Sst2

G protein–coupled receptor (GPCR) signaling is fundamental to physiological processes such as vision, the immune response, and wound healing. In the budding yeast Saccharomyces cerevisiae, GPCRs detect and respond to gradients of pheromone during mating. After pheromone stimulation, the GPCR Ste2 is...

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Autores principales: Venkatapurapu, Sai Phanindra, Kelley, Joshua B., Dixit, Gauri, Pena, Matthew, Errede, Beverly, Dohlman, Henrik G., Elston, Timothy C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710242/
https://www.ncbi.nlm.nih.gov/pubmed/26310439
http://dx.doi.org/10.1091/mbc.E14-12-1635
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author Venkatapurapu, Sai Phanindra
Kelley, Joshua B.
Dixit, Gauri
Pena, Matthew
Errede, Beverly
Dohlman, Henrik G.
Elston, Timothy C.
author_facet Venkatapurapu, Sai Phanindra
Kelley, Joshua B.
Dixit, Gauri
Pena, Matthew
Errede, Beverly
Dohlman, Henrik G.
Elston, Timothy C.
author_sort Venkatapurapu, Sai Phanindra
collection PubMed
description G protein–coupled receptor (GPCR) signaling is fundamental to physiological processes such as vision, the immune response, and wound healing. In the budding yeast Saccharomyces cerevisiae, GPCRs detect and respond to gradients of pheromone during mating. After pheromone stimulation, the GPCR Ste2 is removed from the cell membrane, and new receptors are delivered to the growing edge. The regulator of G protein signaling (RGS) protein Sst2 acts by accelerating GTP hydrolysis and facilitating pathway desensitization. Sst2 is also known to interact with the receptor Ste2. Here we show that Sst2 is required for proper receptor recovery at the growing edge of pheromone-stimulated cells. Mathematical modeling suggested pheromone-induced synthesis of Sst2 together with its interaction with the receptor function to reestablish a receptor pool at the site of polarized growth. To validate the model, we used targeted genetic perturbations to selectively disrupt key properties of Sst2 and its induction by pheromone. Together our results reveal that a regulator of G protein signaling can also regulate the G protein–coupled receptor. Whereas Sst2 negatively regulates G protein signaling, it acts in a positive manner to promote receptor retention at the growing edge.
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spelling pubmed-47102422016-01-20 Modulation of receptor dynamics by the regulator of G protein signaling Sst2 Venkatapurapu, Sai Phanindra Kelley, Joshua B. Dixit, Gauri Pena, Matthew Errede, Beverly Dohlman, Henrik G. Elston, Timothy C. Mol Biol Cell Articles G protein–coupled receptor (GPCR) signaling is fundamental to physiological processes such as vision, the immune response, and wound healing. In the budding yeast Saccharomyces cerevisiae, GPCRs detect and respond to gradients of pheromone during mating. After pheromone stimulation, the GPCR Ste2 is removed from the cell membrane, and new receptors are delivered to the growing edge. The regulator of G protein signaling (RGS) protein Sst2 acts by accelerating GTP hydrolysis and facilitating pathway desensitization. Sst2 is also known to interact with the receptor Ste2. Here we show that Sst2 is required for proper receptor recovery at the growing edge of pheromone-stimulated cells. Mathematical modeling suggested pheromone-induced synthesis of Sst2 together with its interaction with the receptor function to reestablish a receptor pool at the site of polarized growth. To validate the model, we used targeted genetic perturbations to selectively disrupt key properties of Sst2 and its induction by pheromone. Together our results reveal that a regulator of G protein signaling can also regulate the G protein–coupled receptor. Whereas Sst2 negatively regulates G protein signaling, it acts in a positive manner to promote receptor retention at the growing edge. The American Society for Cell Biology 2015-11-05 /pmc/articles/PMC4710242/ /pubmed/26310439 http://dx.doi.org/10.1091/mbc.E14-12-1635 Text en © 2015 Venkatapurapu, Kelley, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Venkatapurapu, Sai Phanindra
Kelley, Joshua B.
Dixit, Gauri
Pena, Matthew
Errede, Beverly
Dohlman, Henrik G.
Elston, Timothy C.
Modulation of receptor dynamics by the regulator of G protein signaling Sst2
title Modulation of receptor dynamics by the regulator of G protein signaling Sst2
title_full Modulation of receptor dynamics by the regulator of G protein signaling Sst2
title_fullStr Modulation of receptor dynamics by the regulator of G protein signaling Sst2
title_full_unstemmed Modulation of receptor dynamics by the regulator of G protein signaling Sst2
title_short Modulation of receptor dynamics by the regulator of G protein signaling Sst2
title_sort modulation of receptor dynamics by the regulator of g protein signaling sst2
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710242/
https://www.ncbi.nlm.nih.gov/pubmed/26310439
http://dx.doi.org/10.1091/mbc.E14-12-1635
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