Analysis of localized cAMP perturbations within a tissue reveal the effects of a local, dynamic gap junction state on ERK signaling.
PLoS Comput Biol
; 18(3): e1009873, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35353814
ABSTRACT
Beyond natural stimuli such as growth factors and stresses, the ability to experimentally modulate at will the levels or activity of specific intracellular signaling molecule(s) in specified cells within a tissue can be a powerful tool for uncovering new regulation and tissue behaviors. Here we perturb the levels of cAMP within specific cells of an epithelial monolayer to probe the time-dynamic behavior of cell-cell communication protocols implemented by the cAMP/PKA pathway and its coupling to the ERK pathway. The time-dependent ERK responses we observe in the perturbed cells for spatially uniform cAMP perturbations (all cells) can be very different from those due to spatially localized perturbations (a few cells). Through a combination of pharmacological and genetic perturbations, signal analysis, and computational modeling, we infer how intracellular regulation and regulated cell-cell coupling each impact the intracellular ERK response in single cells. Our approach reveals how a dynamic gap junction state helps sculpt the intracellular ERK response over time in locally perturbed cells.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Quinases Dependentes de AMP Cíclico
/
AMP Cíclico
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
PLoS Comput Biol
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Portugal