Artículo

Pesce, C.G.; Zdraljevic, S.; Peria, W.J.; Bush, A.; Repetto, M.V.; Rockwell, D.; Yu, R.C.; Colman-Lerner, A.; Brent, R. "Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling" (2018) Molecular Systems Biology. 14(4)
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Abstract:

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

Registro:

Documento: Artículo
Título:Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling
Autor:Pesce, C.G.; Zdraljevic, S.; Peria, W.J.; Bush, A.; Repetto, M.V.; Rockwell, D.; Yu, R.C.; Colman-Lerner, A.; Brent, R.
Filiación:Abalone Bio, Inc., Richmond, CA, United States
Department of Molecular Biosciences, Northwestern University, Evanston, IL, United States
Fred Hutchinson Cancer Research Center, Seattle, WA, United States
IFIBYNE-UBA-CONICET and Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave: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
Año:2018
Volumen:14
Número:4
DOI: http://dx.doi.org/10.15252/msb.20167390
Título revista:Molecular Systems Biology
Título revista abreviado:Mol. Syst. Biol.
ISSN:17444292
CAS:mitogen activated protein kinase, 142243-02-5; Adaptor Proteins, Signal Transducing; BIM1 protein, S cerevisiae; Cell Cycle Proteins; FUS3 protein, S cerevisiae; Microtubule Proteins; Mitogen-Activated Protein Kinases; Pheromones; Saccharomyces cerevisiae Proteins; STE5 protein, S cerevisiae
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17444292_v14_n4_p_Pesce

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Citas:

---------- APA ----------
Pesce, C.G., Zdraljevic, S., Peria, W.J., Bush, A., Repetto, M.V., Rockwell, D., Yu, R.C.,..., Brent, R. (2018) . Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling. Molecular Systems Biology, 14(4).
http://dx.doi.org/10.15252/msb.20167390
---------- CHICAGO ----------
Pesce, C.G., Zdraljevic, S., Peria, W.J., Bush, A., Repetto, M.V., Rockwell, D., et al. "Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling" . Molecular Systems Biology 14, no. 4 (2018).
http://dx.doi.org/10.15252/msb.20167390
---------- MLA ----------
Pesce, C.G., Zdraljevic, S., Peria, W.J., Bush, A., Repetto, M.V., Rockwell, D., et al. "Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling" . Molecular Systems Biology, vol. 14, no. 4, 2018.
http://dx.doi.org/10.15252/msb.20167390
---------- VANCOUVER ----------
Pesce, C.G., Zdraljevic, S., Peria, W.J., Bush, A., Repetto, M.V., Rockwell, D., et al. Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling. Mol. Syst. Biol. 2018;14(4).
http://dx.doi.org/10.15252/msb.20167390