Interlinked fast and slow positive feedback loops drive reliable cell decisions

Abstract

Positive feedback is a ubiquitous signal transduction motif that allows systems to convert graded inputs into decisive, all-or-none outputs. Here we investigate why the positive feedback switches that regulate polarization of budding yeast, calcium signaling, Xenopus oocyte maturation, and various other processes use multiple interlinked loops rather than single positive feedback loops. Mathematical simulations revealed that linking fast and slow positive feedback loops creates a "dual-time" switch that is both rapidly inducible and resistant to noise in the upstream signaling system.

Fig. 1

Schematic views of positive feedback loops in three systems. (A) Establishment of polarity in budding yeast. (B) Mammalian calcium signal transduction. (C) Xenopus oocyte maturation.

Fig. 2

Calculated responses of single and dual positive feedback loop switches to stimuli. (A) A one-loop switch. (B) A two-loop switch. (C to G) Feedback loop output (y axis) as a function of time (x axis) for single-loop and two-loop switches. (C) One slow loop. (D) Two slow loops. (E) One fast loop. (F) Two fast loops. (G) One slow loop and one fast loop. The curves on the left assume a noise-free stimulus; the curves on the right assume a noisy stimulus.