Abstract:
:Natural environments are filled with multiple, often competing, signals. In contrast, biological systems are often studied in "well-controlled" environments where only a single input is varied, potentially missing important interactions between signals. Catabolite repression of galactose by glucose is one of the best-studied eukaryotic signal integration systems. In this system, it is believed that galactose metabolic (GAL) genes are induced only when glucose levels drop below a threshold. In contrast, we show that GAL gene induction occurs at a constant external galactose:glucose ratio across a wide range of sugar concentrations. We systematically perturbed the components of the canonical galactose/glucose signaling pathways and found that these components do not account for ratio sensing. Instead we provide evidence that ratio sensing occurs upstream of the canonical signaling pathway and results from the competitive binding of the two sugars to hexose transporters. We show that a mutant that behaves as the classical model expects (i.e., cannot use galactose above a glucose threshold) has a fitness disadvantage compared with wild type. A number of common biological signaling motifs can give rise to ratio sensing, typically through negative interactions between opposing signaling molecules. We therefore suspect that this previously unidentified nutrient sensing paradigm may be common and overlooked in biology.
journal_name
Proc Natl Acad Sci U S Aauthors
Escalante-Chong R,Savir Y,Carroll SM,Ingraham JB,Wang J,Marx CJ,Springer Mdoi
10.1073/pnas.1418058112subject
Has Abstractpub_date
2015-02-03 00:00:00pages
1636-41issue
5eissn
0027-8424issn
1091-6490pii
1418058112journal_volume
112pub_type
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