ArticleMolecular systems biology2016
Yeast GPCR signaling reflects the fraction of occupied receptors, not the number.
Article in Molecular systems biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Ratiometric signaling produces robust temporal integration for accurate cellular gradient sensing.bioRxiv : the preprint server for biology · 2026Article
- A yeast mating platform for multiplex screening of fungal GPCR-ligand interactions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Individual yeast cells signal at different levels but each with good precision.Royal Society open science · 2025Article
- GPCR Sense Communication Among Interaction Nematodes with Other Organisms.International journal of molecular sciences · 2025Review
- Amplitude and frequency encoding result in qualitatively distinct informational landscapes in cell signaling.Scientific reports · 2025Article
- Design patterns of biological cells.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- Design principles of improving the dose-response alignment in coupled GTPase switches.NPJ systems biology and applications · 2023Article
- A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination.Nature communications · 2022Article
- Dynamics and Sensitivity of Signaling Pathways.Current pathobiology reports · 2022Article
- Orientation of Cell Polarity by Chemical Gradients.Annual review of biophysics · 2022Review
- Molecular switch architecture determines response properties of signaling pathways.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- GPCR receptor phosphorylation and endocytosis are not necessary to switch polarized growth between internal cues during pheromone response inCommunicative & integrative biology · 2020Article
- Efficient manipulation and generation of Kirchhoff polynomials for the analysis of non-equilibrium biochemical reaction networks.Journal of the Royal Society, Interface · 2020Article
- Engineering G protein-coupled receptor signalling in yeast for biotechnological and medical purposes.FEMS yeast research · 2020Review
- Ratiometric GPCR signaling enables directional sensing in yeast.PLoS biology · 2019Article
- Article
- Transferring information without distortion.eLife · 2018Article
- Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling.Molecular systems biology · 2018Article
- Analysis of the thresholds for transcriptional activation by the yeast MAP kinases Fus3 and Kss1.Molecular biology of the cell · 2018Article
- The directed evolution of ligand specificity in a GPCR and the unequal contributions of efficacy and affinity.Scientific reports · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
According to receptor theory, the effect of a ligand depends on the amount of agonist-receptor complex. Therefore, changes in receptor abundance should have quantitative effects. However, the response to pheromone in Saccharomyces cerevisiae is robust (unaltered) to increases or reductions in the abundance of the G-protein-coupled receptor (GPCR), Ste2, responding instead to the fraction of occupied receptor. We found experimentally that this robustness originates during G-protein activation. We developed a complete mathematical model of this step, which suggested the ability to compute fractional occupancy depends on the physical interaction between the inhibitory regulator of G-protein signaling (RGS), Sst2, and the receptor. Accordingly, replacing Sst2 by the heterologous hsRGS4, incapable of interacting with the receptor, abolished robustness. Conversely, forcing hsRGS4:Ste2 interaction restored robustness. Taken together with other results of our work, we conclude that this GPCR pathway computes fractional occupancy because ligand-bound GPCR-RGS complexes stimulate signaling while unoccupied complexes actively inhibit it. In eukaryotes, many RGSs bind to specific GPCRs, suggesting these complexes with opposing activities also detect fraction occupancy by a ratiometric measurement. Such complexes operate as push-pull devices, which we have recently described.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.