A systems-level analysis of perfect adaptation in yeast osmoregulation
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Van oudenaarden_A systems-level.pdf
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2.05 MB
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Author(s)
Muzzey, Dale
Gomez-Uribe, Carlos A.
Mettetal, Jerome T.
van Oudenaarden, Alexander
Date Issued
July 2009
Journal
Cell
Publisher
Elsevier B.V.
Citation
Muzzey, Dale et al. “A Systems-Level Analysis of Perfect Adaptation in Yeast Osmoregulation.” Cell 138.1 (2009): 160–171. Web.
Version
Author's final manuscript
Abstract
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.
Description
available in PMC 2011 June 7.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1016/j.cell.2009.04.047
