Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling
- Autores
- Pesce, Gustavo C.; Zdraljevic, Stefan; Peria, William J.; Bush, Alan; Repetto, María Victoria; Rockwell, Daniel; Yu, Richard C.; Colman Lerner, Alejandro Ariel; Brent, Roger
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Pesce, Gustavo C.. Abalone Bio, Inc; Estados Unidos
Fil: Zdraljevic, Stefan. Northwestern University; Estados Unidos
Fil: Peria, William J.. Fred Hutchinson Cancer Research Center; Estados Unidos
Fil: Bush, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Repetto, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Rockwell, Daniel. Abalone Bio Inc; Estados Unidos
Fil: Yu, Richard C.. Abalone Bio Inc; Estados Unidos
Fil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Brent, Roger. Fred Hutchinson Cancer Research Center; Estados Unidos - Materia
-
CELL-TO-CELL VARIABILITY
GENETIC SCREEN
MAP KINASE
MICROTUBULES
NOISE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/89279
Ver los metadatos del registro completo
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spelling |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signalingPesce, Gustavo C.Zdraljevic, StefanPeria, William J.Bush, AlanRepetto, María VictoriaRockwell, DanielYu, Richard C.Colman Lerner, Alejandro ArielBrent, RogerCELL-TO-CELL VARIABILITYGENETIC SCREENMAP KINASEMICROTUBULESNOISEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Populations 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.Fil: Pesce, Gustavo C.. Abalone Bio, Inc; Estados UnidosFil: Zdraljevic, Stefan. Northwestern University; Estados UnidosFil: Peria, William J.. Fred Hutchinson Cancer Research Center; Estados UnidosFil: Bush, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Repetto, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Rockwell, Daniel. Abalone Bio Inc; Estados UnidosFil: Yu, Richard C.. Abalone Bio Inc; Estados UnidosFil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Brent, Roger. Fred Hutchinson Cancer Research Center; Estados UnidosNature Publishing Group2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/89279Pesce, Gustavo C.; Zdraljevic, Stefan; Peria, William J.; Bush, Alan; Repetto, María Victoria; et al.; Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling; Nature Publishing Group; Molecular Systems Biology; 14; 4; 4-2018; 1-201744-4292CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.embopress.org/doi/full/10.15252/msb.20167390info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884679/info:eu-repo/semantics/altIdentifier/doi/10.15252/msb.20167390info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:37:03Zoai:ri.conicet.gov.ar:11336/89279instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:37:03.886CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
title |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling |
spellingShingle |
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling Pesce, Gustavo C. CELL-TO-CELL VARIABILITY GENETIC SCREEN MAP KINASE MICROTUBULES NOISE |
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 |
dc.creator.none.fl_str_mv |
Pesce, Gustavo C. Zdraljevic, Stefan Peria, William J. Bush, Alan Repetto, María Victoria Rockwell, Daniel Yu, Richard C. Colman Lerner, Alejandro Ariel Brent, Roger |
author |
Pesce, Gustavo C. |
author_facet |
Pesce, Gustavo C. Zdraljevic, Stefan Peria, William J. Bush, Alan Repetto, María Victoria Rockwell, Daniel Yu, Richard C. Colman Lerner, Alejandro Ariel Brent, Roger |
author_role |
author |
author2 |
Zdraljevic, Stefan Peria, William J. Bush, Alan Repetto, María Victoria Rockwell, Daniel Yu, Richard C. Colman Lerner, Alejandro Ariel Brent, Roger |
author2_role |
author author author author author author author author |
dc.subject.none.fl_str_mv |
CELL-TO-CELL VARIABILITY GENETIC SCREEN MAP KINASE MICROTUBULES NOISE |
topic |
CELL-TO-CELL VARIABILITY GENETIC SCREEN MAP KINASE MICROTUBULES NOISE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
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. Fil: Pesce, Gustavo C.. Abalone Bio, Inc; Estados Unidos Fil: Zdraljevic, Stefan. Northwestern University; Estados Unidos Fil: Peria, William J.. Fred Hutchinson Cancer Research Center; Estados Unidos Fil: Bush, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Repetto, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Rockwell, Daniel. Abalone Bio Inc; Estados Unidos Fil: Yu, Richard C.. Abalone Bio Inc; Estados Unidos Fil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Brent, Roger. Fred Hutchinson Cancer Research Center; Estados Unidos |
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. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-04 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/89279 Pesce, Gustavo C.; Zdraljevic, Stefan; Peria, William J.; Bush, Alan; Repetto, María Victoria; et al.; Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling; Nature Publishing Group; Molecular Systems Biology; 14; 4; 4-2018; 1-20 1744-4292 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/89279 |
identifier_str_mv |
Pesce, Gustavo C.; Zdraljevic, Stefan; Peria, William J.; Bush, Alan; Repetto, María Victoria; et al.; Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling; Nature Publishing Group; Molecular Systems Biology; 14; 4; 4-2018; 1-20 1744-4292 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.embopress.org/doi/full/10.15252/msb.20167390 info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884679/ info:eu-repo/semantics/altIdentifier/doi/10.15252/msb.20167390 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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