A systems-level analysis of perfect adaptation in yeast osmoregulation.
Negative feedback can serve many different cellular functions, including noise reduction in transcriptional networks and the creation of circadian oscillations. However, only one special type of negative feedback ("integral feedback") ensures perfect adaptation, where steady-state output is independent of steady-state input. Here we quantitatively measure single-cell dynamics in the Saccharomyces cerevisiae hyperosmotic shock network, which regulates membrane turgor pressure. Importantly, we find that the nuclear enrichment of the MAP kinase Hog1 perfectly adapts to changes in external osmolarity, a feature robust to signaling fidelity and operating with very low noise. By monitoring multiple system quantities (e.g., cell volume, Hog1, glycerol) and using varied input waveforms (e.g., steps and ramps), we assess in a minimally invasive manner the network location of the mechanism responsible for perfect adaptation. We conclude that the system contains only one effective integrating mechanism, which requires Hog1 kinase activity and regulates glycerol synthesis but not leakage.
Muzzey
Dale
D
Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Gómez-Uribe
Carlos A
CA
Mettetal
Jerome T
JT
van Oudenaarden
Alexander
A
D002467:Cell Nucleus / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005990:Glycerol / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009997:Osmotic Pressure; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014882:Water-Electrolyte Balance
D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D005990:Glycerol