(612b) The Low-Pass Filtering Effect of Degradation-Driven Protein Turnover

A low-pass filter passes low-frequency signals while attenuating high-frequency ones. To remove high-frequency noise, low-pass filtering is widely used in science and engineering. Low-pass filtering behavior is also found in various biological systems, which allow robust adaptation to continuously changing environment. Since the intracellular environment is highly stochastic, reduction of high frequency noise is critical in maintaining homeostasis and on the other hand allowing efficient adaptation. Previous studies have reported low-pass filtering in the cellular transcription machinery, using fluctuating levels of galactose inducer with defined frequency. The other side of protein turnover is protein degradation, and continual balance between production and degradation results in observed protein levels in cells. Here, we hypothesized that protein degradation driven protein turnover also filters out high-frequency fluctuations. To experimentally validate this, we applied a light-activated protein degradation machinery, which enables fluctuations in protein degradation rate by delivering temporally controlled light stimulation. This optogenetic approach allowed us to observe degradation-driven fluctuations in fluorescent reporter protein levels in the yeast Saccharomyces cerevisiae. We show that under continuous transcription (as assessed by quantitative PCR of the transcript), the protein level fluctuates according to the light stimulation at frequencies (1/f) ranging from 100 min to 20 min. As stimulation frequency increases, the delay between input (light stimulation) and output (protein level) increases and the amplitude of fluctuation decreases. These characteristic behaviors of low-pass filtering indicate that the degradation machinery also filters out high frequency noise, but respond robustly to slow fluctuations with response times faster than that of the transcription machinery. Our results combined with previous studies conclude that both protein production and degradation enable protein turnover to exhibit low-pass filtering.