title: Modulation of receptor dynamics by the regulator of G protein signaling Sst2.
abstract: 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.
authors: Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Sai Phanindra
authors: SP
authors: Venkatapurapu
authors: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Joshua B
authors: JB
authors: Kelley
authors: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Gauri
authors: G
authors: Dixit
authors: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Matthew
authors: M
authors: Pena
authors: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Beverly
authors: B
authors: Errede
authors: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 timothy_elston@med.unc.edu henrik_dohlman@med.unc.edu.
authors: Henrik G
authors: HG
authors: Dohlman
authors: Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 timothy_elston@med.unc.edu henrik_dohlman@med.unc.edu.
authors: Timothy C
authors: TC
authors: Elston
mesh_terms: D000595:Amino Acid Sequence; D004705:Endocytosis; D020555:GTP-Binding Protein Regulators / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D008954:Models, Biological; D010675:Pheromones / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D020710:RGS Proteins
chemical_list: D020555:GTP-Binding Protein Regulators; D020690:GTPase-Activating Proteins; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C094301:SST2 protein, S cerevisiae; D020710:RGS Proteins