Bistable modules ensure two different types of oscillatory behavior in signaling cascades

JUAN IGNACIO MARRONE; JACQUES-A. SEPULCHRE; ALEJANDRA C VENTURA

Conferencia; Dynamics Days Digital 2020 (DDD2020); 2020

In this work we focus on signalingsystems with no explicit negative feedback (NF) and a structure ensuringbistability, like a double phosphorylation cycle. It is established thatbistability is possible due to an underlying positive feedback (PF). We studyminimal additions to the system, representing its connection with a signalingpathway, like the activation of an enzyme or the modified substrates beinginvolved in other reactions. This produces sequestration of the proteins in thecycle, in turn producing a (not explicit) NF. The result is a minimal signalingsystem combining both PF and NF. This has been shown to generaterelaxation-type oscillations. We show that both feedbacks together also ensurea smooth type of oscillations in a narrow range of frequencies, and even more,that both feedbacks are essential for both oscillatory types to emerge,depending on the hierarchy of feedbacks. We developed tools to classify theoscillations and applied these ideas on simpler models to generalize what welearned from signaling models.