期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 14, 页码 E2975-E2982出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1611428114
关键词
signal transduction; fold-change detection; Tgf-beta; Smad; information
资金
- NIH [2T32GM007616-36, 5T32GM007616-37, DP2OD008471]
- James S. McDonnell Scholar Award in Complex Systems [220020365]
- National Science Foundation [NSF.1453863]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1453863] Funding Source: National Science Foundation
How signaling pathways function reliably despite cellular variation remains a question in many systems. In the transforming growth factor-beta (Tgf-beta) pathway, exposure to ligand stimulates nuclear localization of Smad proteins, which then regulate target gene expression. Examining Smad3 dynamics in live reporter cells, we found evidence for fold-change detection. Although the level of nuclear Smad3 varied across cells, the fold change in the level of nuclear Smad3 was a more precise outcome of ligand stimulation. The precision of the fold-change response was observed throughout the signaling duration and across Tgf-beta doses, and significantly increased the information transduction capacity of the pathway. Using single-molecule FISH, we further observed that expression of Smad3 target genes (ctgf, snai1, and wnt9a) correlated more strongly with the fold change, rather than the level, of nuclear Smad3. These findings suggest that some target genes sense Smad3 level relative to background, as a strategy for coping with cellular noise.
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