The regulatory circuits for hysteretic switching in cellular signal transduction pathways
Abstract
Hysteresis can be found in many physical systems, and a hysteretic switch has been used for various mechanical and electrical systems. Such a hysteretic switch can be created by using a single positive feedback loop, as often used in engineering systems. It is, however, intriguing that various cellular signaling systems use coupled positive feedback loops to implement the hysteretic switch. A question then arises about the advantage of using coupled positive feedback loops instead of simple isolated positive feedback for an apparently equivalent hysteretic switch. Through mathematical simulations, we determined that cellular systems with coupled positive feedback loops show enhanced hysteretic switching, and can thereby make a more reliable decision under conditions of noisy signaling. As most intracellular processes are accompanied by intrinsic noise, important cellular decisions such as differentiation and apoptosis need to be highly robust to such noises. The coupled positive feedback loops might have been evolutionarily acquired to enable correct cell fate decisions to be made through enhanced hysteretic switching in noisy cellular environments.
References
The JNK cascade as a biochemical switch in mammalian cells: ultrasensitive and all-or-none responses
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis