Diverse roles of guanine nucleotide exchange factors in regulating collective cell migration.

Zaritsky, Assaf; Tseng, Yun-Yu; Rabadán, M Angeles; Krishna, Shefali; Overholtzer, Michael; Danuser, Gaudenz; Hall, Alan

Zaritsky, Assaf; Tseng, Yun-Yu; Rabadán, M Angeles; Krishna, Shefali; Overholtzer, Michael; Danuser, Gaudenz; Hall, Alan.

Afiliación

Zaritsky A; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Tseng YY; Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Rabadán MA; Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
Krishna S; Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
Overholtzer M; Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
Danuser G; Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 gaudenz.danuser@utsouthwestern.edu overhom1@mskcc.org.
Hall A; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 gaudenz.danuser@utsouthwestern.edu overhom1@mskcc.org.

J Cell Biol ; 216(6): 1543-1556, 2017 06 05.

Article en En | MEDLINE | ID: mdl-28512143

RESUMEN

Efficient collective migration depends on a balance between contractility and cytoskeletal rearrangements, adhesion, and mechanical cell-cell communication, all controlled by GTPases of the RHO family. By comprehensive screening of guanine nucleotide exchange factors (GEFs) in human bronchial epithelial cell monolayers, we identified GEFs that are required for collective migration at large, such as SOS1 and ß-PIX, and RHOA GEFs that are implicated in intercellular communication. Down-regulation of the latter GEFs differentially enhanced front-to-back propagation of guidance cues through the monolayer and was mirrored by down-regulation of RHOA expression and myosin II activity. Phenotype-based clustering of knockdown behaviors identified RHOA-ARHGEF18 and ARHGEF3-ARHGEF28-ARHGEF11 clusters, indicating that the latter may signal through other RHO-family GTPases. Indeed, knockdown of RHOC produced an intermediate between the two phenotypes. We conclude that for effective collective migration, the RHOA-GEFs â RHOA/C â actomyosin pathways must be optimally tuned to compromise between generation of motility forces and restriction of intercellular communication.

Asunto(s)

Bronquios/enzimología; Movimiento Celular; Células Epiteliales/enzimología; Factores de Intercambio de Guanina Nucleótido/metabolismo; Transducción de Señal; Proteínas de Unión al GTP rho/metabolismo; Proteína de Unión al GTP rhoA/metabolismo; Actomiosina/metabolismo; Bronquios/citología; Línea Celular; Factores de Intercambio de Guanina Nucleótido/genética; Humanos; Fenotipo; Interferencia de ARN; Factores de Intercambio de Guanina Nucleótido Rho/genética; Factores de Intercambio de Guanina Nucleótido Rho/metabolismo; Proteína SOS1/genética; Proteína SOS1/metabolismo; Factores de Tiempo; Transfección; Cicatrización de Heridas; Proteínas de Unión al GTP rho/genética; Proteína de Unión al GTP rhoA/genética; Proteína rhoC de Unión a GTP

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bronquios / Transducción de Señal / Movimiento Celular / Proteínas de Unión al GTP rho / Proteína de Unión al GTP rhoA / Factores de Intercambio de Guanina Nucleótido / Células Epiteliales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Cell Biol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos

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