Abstract：
:It is known that the calcium-dependent transcription factor NFAT initiates transcription in response to pulsatile loads of calcium signal. However, the relative contributions of calcium oscillation frequency, amplitude, and duty cycle to transcriptional activity remain unclear. Here, we engineer HeLa cells to permit optogenetic control of intracellular calcium concentration using programmable LED arrays. This approach allows us to generate calcium oscillations of constant peak amplitude, in which frequency is varied while holding duty cycle constant, or vice versa. Using this setup and mathematical modeling, we show that NFAT transcriptional activity depends more on duty cycle, defined as the proportion of the integrated calcium concentration over the oscillation period, than on frequency alone. This demonstrates that NFAT acts primarily as a signal integrator of cumulative load rather than a frequency-selective decoder. This approach resolves a fundamental question in calcium encoding and demonstrates the value of optogenetics for isolating individual dynamical components of larger signaling behaviors.
journal_name
Cell Systjournal_title
Cell systemsauthors
Hannanta-Anan P,Chow BYdoi
10.1016/j.cels.2016.03.010subject
Has Abstractpub_date
2016-04-27 00:00:00pages
283-8issue
4eissn
2405-4712issn
2405-4720pii
S2405-4712(16)30108-9journal_volume
2pub_type
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