This model is from the article: Parallel adaptive feedback enhances reliability of the Ca2+ signaling system. Abell E, Ahrends R, Bandara S, Park BO, Teruel MN. Proc Natl Acad Sci U S A. 2011 Aug 15. 21844332 , Abstract: Despite large cell-to-cell variations in the concentrations of individual signaling proteins, cells transmit signals correctly. This phenomenon raises the question of what signaling systems do to prevent a predicted high failure rate. Here we combine quantitative modeling, RNA interference, and targeted selective reaction monitoring (SRM) mass spectrometry, and we show for the ubiquitous and fundamental calcium signaling system that cells monitor cytosolic and endoplasmic reticulum (ER) Ca(2+) levels and adjust in parallel the concentrations of the store-operated Ca(2+) influx mediator stromal interaction molecule (STIM), the plasma membrane Ca(2+) pump plasma membrane Ca-ATPase (PMCA), and the ER Ca(2+) pump sarco/ER Ca(2+)-ATPase (SERCA). Model calculations show that this combined parallel regulation in protein expression levels effectively stabilizes basal cytosolic and ER Ca(2+) levels and preserves receptor signaling. Our results demonstrate that, rather than directly controlling the relative level of signaling proteins in a forward regulation strategy, cells prevent transmission failure by sensing the state of the signaling pathway and using multiple parallel adaptive feedbacks. Note: There are two models described in the paper to simulate basal and receptor stimulated Ca 2+ signaling. 1) No adaptive feedback (this model: MODEL1108050000) and 2) with three slow adaptive feedback loops (MODEL1108050001).
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305
IP3R: IP3 and Ca2+ regulated Ca2+ channel, plus leak
Inhibition of IP3R (mechanism not well understood)
PLC: Receptor and Ca2+ regulated IP3 production
Recovery of IP3R from Ca2+ iinhibition when Ca2+ drops