FKBP12 determines ligand-specific SMAD signaling in individual living endothelial cells -data
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2026-05-17
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The BMP signaling pathway plays a pivotal role in regulating the formation and maintenance of our vascular system, employing a diverse set of ligands, receptors and cytoplasmic mediators. However, little is known about how the interplay of these elements is regulated dynamically in individual living endothelial cells. Here, we developed fluorescent reporter to quantify BMP signaling and used a combination of time-resolved microscopy and computer-aided analysis to demonstrate ligand-specific dynamics of SMAD1, SMAD5 and SMAD9. Using this approach, we identified FKBP12 as a critical regulator of receptor complex activity that determines the balance of SMAD1/5/9 and SMAD2/3 signaling upon treatment with angiogenic ligands such as BMP7 and Activin A. This provides insights into the regulation of the BMP pathway in endothelial cells and potential therapeutic targets for vascular pathologies.
The datasets were generated by time-resolved microscopy of human EA.hy926 cells expressing a N-terminal fusion of the yellow fluorescent protein mVenus to SMAD1. For some conditions, cells also expressed a N-terminal fusion of the red fluorescent protein mCherry to SMAD2. Datasets comprise ratios of nuclear to cytoplasmic mean fluorescence intensities as well as corresponding time points. Single-cell data can be mapped to experimental treatments as demonstrated by the provided Matlab script. Further details are available in the corresponding publication.
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Except where otherwise noted, this license is described as CC BY 4.0 - Attribution 4.0 International