The regulatory circuits for hysteretic switching in cellular signal transduction pathways

The FEBS Journal
Jeong-Rae Kim, Kwang-Hyun Cho

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.

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Citations

May 17, 2014·Journal of Molecular Cell Biology·Dongkwan ShinKwang-Hyun Cho
Jun 19, 2013·ACS Synthetic Biology·Meng ChenQing Nie
Jan 24, 2017·PLoS Computational Biology·William R HolmesQing Nie
Aug 3, 2018·Nature Communications·So-Young YeoSeok-Hyung Kim
Feb 13, 2021·Current Opinion in Cell Biology·Jordi Berenguer, Toni Celià-Terrassa
May 23, 2021·Bioinformatics·Suvankar HalderSamrat Chatterjee

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