A nested bistable module within a negative feedback loop ensures different types of oscillations in signaling systems.
Sci Rep
; 13(1): 529, 2023 01 11.
Article
em En
| MEDLINE
| ID: mdl-36631477
In this article, we consider a double phosphorylation cycle, a ubiquitous signaling component, having the ability to display bistability, a behavior strongly related to the existence of positive feedback loops. If this component is connected to other signaling elements, it very likely undergoes some sort of protein-protein interaction. In several cases, these interactions result in a non-explicit negative feedback effect, leading to interlinked positive and negative feedbacks. This combination was studied in the literature as a way to generate relaxation-type oscillations. Here, we show that the two feedbacks together ensure two types of oscillations, the relaxation-type ones and a smoother type of oscillations functioning in a very narrow range of frequencies, in such a way that outside that range, the amplitude of the oscillations is severely compromised. Even more, we show that the two feedbacks are essential for both oscillatory types to emerge, and it is their hierarchy what determines the type of oscillation at work. We used bifurcation analyses and amplitude vs. frequency curves to characterize and classify the oscillations. We also applied the same ideas to another simple model, with the goal of generalizing what we learned from signaling models. The results obtained display the wealth of oscillatory dynamics that exists in a system with a bistable module nested within a negative feedback loop, showing how to transition between different types of oscillations and other dynamical behaviors such as excitability. Our work provides a framework for the study of other oscillatory systems based on bistable modules, from simple two-component models to more complex examples like the MAPK cascade and experimental cases like cell cycle oscillators.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Retroalimentação Fisiológica
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Argentina
País de publicação:
Reino Unido