Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling
Populations of isogenic cells often respond coherently to signals, despite differences in protein abundance and cell state. Previously, we uncovered processes in the Saccharomyces cerevisiae pheromone response system (PRS) that reduced cell-to-cell variability in signal strength and cellular respons...
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2018
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17444292_v14_n4_p_Pesce http://hdl.handle.net/20.500.12110/paper_17444292_v14_n4_p_Pesce |
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paper:paper_17444292_v14_n4_p_Pesce2023-06-08T16:28:12Z Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling cell-to-cell variability genetic screen MAP kinase microtubules noise BIM1 protein, S cerevisiae cell cycle protein FUS3 protein, S cerevisiae microtubule protein mitogen activated protein kinase pheromone Saccharomyces cerevisiae protein signal transducing adaptor protein STE5 protein, S cerevisiae genetics MAPK signaling metabolism microtubule Saccharomyces cerevisiae signal transduction single cell analysis Adaptor Proteins, Signal Transducing Cell Cycle Proteins MAP Kinase Signaling System Microtubule Proteins Microtubules Mitogen-Activated Protein Kinases Pheromones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Single-Cell Analysis Populations of isogenic cells often respond coherently to signals, despite differences in protein abundance and cell state. Previously, we uncovered processes in the Saccharomyces cerevisiae pheromone response system (PRS) that reduced cell-to-cell variability in signal strength and cellular response. Here, we screened 1,141 non-essential genes to identify 50 “variability genes”. Most had distinct, separable effects on strength and variability of the PRS, defining these quantities as genetically distinct “axes” of system behavior. Three genes affected cytoplasmic microtubule function: BIM1, GIM2, and GIM4. We used genetic and chemical perturbations to show that, without microtubules, PRS output is reduced but variability is unaffected, while, when microtubules are present but their function is perturbed, output is sometimes lowered, but its variability is always high. The increased variability caused by microtubule perturbations required the PRS MAP kinase Fus3 and a process at or upstream of Ste5, the membrane-localized scaffold to which Fus3 must bind to be activated. Visualization of Ste5 localization dynamics demonstrated that perturbing microtubules destabilized Ste5 at the membrane signaling site. The fact that such microtubule perturbations cause aberrant fate and polarity decisions in mammals suggests that microtubule-dependent signal stabilization might also operate throughout metazoans. © 2018 The Authors. Published under the terms of the CC BY 4.0 license 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17444292_v14_n4_p_Pesce http://hdl.handle.net/20.500.12110/paper_17444292_v14_n4_p_Pesce |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
cell-to-cell variability genetic screen MAP kinase microtubules noise BIM1 protein, S cerevisiae cell cycle protein FUS3 protein, S cerevisiae microtubule protein mitogen activated protein kinase pheromone Saccharomyces cerevisiae protein signal transducing adaptor protein STE5 protein, S cerevisiae genetics MAPK signaling metabolism microtubule Saccharomyces cerevisiae signal transduction single cell analysis Adaptor Proteins, Signal Transducing Cell Cycle Proteins MAP Kinase Signaling System Microtubule Proteins Microtubules Mitogen-Activated Protein Kinases Pheromones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Single-Cell Analysis |
| spellingShingle |
cell-to-cell variability genetic screen MAP kinase microtubules noise BIM1 protein, S cerevisiae cell cycle protein FUS3 protein, S cerevisiae microtubule protein mitogen activated protein kinase pheromone Saccharomyces cerevisiae protein signal transducing adaptor protein STE5 protein, S cerevisiae genetics MAPK signaling metabolism microtubule Saccharomyces cerevisiae signal transduction single cell analysis Adaptor Proteins, Signal Transducing Cell Cycle Proteins MAP Kinase Signaling System Microtubule Proteins Microtubules Mitogen-Activated Protein Kinases Pheromones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Single-Cell Analysis Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
| topic_facet |
cell-to-cell variability genetic screen MAP kinase microtubules noise BIM1 protein, S cerevisiae cell cycle protein FUS3 protein, S cerevisiae microtubule protein mitogen activated protein kinase pheromone Saccharomyces cerevisiae protein signal transducing adaptor protein STE5 protein, S cerevisiae genetics MAPK signaling metabolism microtubule Saccharomyces cerevisiae signal transduction single cell analysis Adaptor Proteins, Signal Transducing Cell Cycle Proteins MAP Kinase Signaling System Microtubule Proteins Microtubules Mitogen-Activated Protein Kinases Pheromones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Single-Cell Analysis |
| description |
Populations of isogenic cells often respond coherently to signals, despite differences in protein abundance and cell state. Previously, we uncovered processes in the Saccharomyces cerevisiae pheromone response system (PRS) that reduced cell-to-cell variability in signal strength and cellular response. Here, we screened 1,141 non-essential genes to identify 50 “variability genes”. Most had distinct, separable effects on strength and variability of the PRS, defining these quantities as genetically distinct “axes” of system behavior. Three genes affected cytoplasmic microtubule function: BIM1, GIM2, and GIM4. We used genetic and chemical perturbations to show that, without microtubules, PRS output is reduced but variability is unaffected, while, when microtubules are present but their function is perturbed, output is sometimes lowered, but its variability is always high. The increased variability caused by microtubule perturbations required the PRS MAP kinase Fus3 and a process at or upstream of Ste5, the membrane-localized scaffold to which Fus3 must bind to be activated. Visualization of Ste5 localization dynamics demonstrated that perturbing microtubules destabilized Ste5 at the membrane signaling site. The fact that such microtubule perturbations cause aberrant fate and polarity decisions in mammals suggests that microtubule-dependent signal stabilization might also operate throughout metazoans. © 2018 The Authors. Published under the terms of the CC BY 4.0 license |
| title |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
| title_short |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
| title_full |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
| title_fullStr |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
| title_full_unstemmed |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
| title_sort |
single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17444292_v14_n4_p_Pesce http://hdl.handle.net/20.500.12110/paper_17444292_v14_n4_p_Pesce |
| _version_ |
1768542476028608512 |