
pmid: 30611092
Several proteins are sensitive to frequency-modulated oscillations of calcium levels. Most of them exhibit increased activities for faster frequencies, a characteristic here referred to as high-pass activation. In contrast, the transcription factor NFAT is optimally activated at a specific frequency, a behaviour we call band-pass activation. We constructed a kinetic model of NFAT activation, confirming its ability for band-pass activation at experimentally observed frequencies. To characterise the requirements for band-pass activation further, we developed a minimal model, identifying antagonistic, calcium-dependent regulation with differently responsive regulators as essential for band-pass activation. Further, in optimisations cooperative binding proved to be an important feature for distinct frequency-decoding in models of high- and band-pass activation. A subsequent analysis of the optimised parameter sets revealed the most sensitive parameters along with additional preconditions for efficient decoding. Our analysis is not limited to NFAT, but potentially applies to any protein showing high- or band-pass activation.
NFATC Transcription Factors, Calcineurin, Models, Biological, Kinetics, Calmodulin, Gene Expression Regulation, Animals, Humans, Calcium, Calcium Signaling, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Protein Kinase C
NFATC Transcription Factors, Calcineurin, Models, Biological, Kinetics, Calmodulin, Gene Expression Regulation, Animals, Humans, Calcium, Calcium Signaling, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Protein Kinase C
| selected citations These citations are derived from selected sources. This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 4 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Average | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Average | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Average |
