Co-imaging of RelA and c-Rel reveals features of NF-κB signaling for ligand discrimination

Shah Md Toufiqur Rahman; Apeksha Singh; Sarina Lowe; Mohammad Aqdas; Kevin Jiang; Haripriya Vaidehi Narayanan; Alexander Hoffmann; Myong-Hee Sung

Cell Reports (Mar 2024)

Co-imaging of RelA and c-Rel reveals features of NF-κB signaling for ligand discrimination

Shah Md Toufiqur Rahman,
Apeksha Singh,
Sarina Lowe,
Mohammad Aqdas,
Kevin Jiang,
Haripriya Vaidehi Narayanan,
Alexander Hoffmann,
Myong-Hee Sung

Affiliations

Shah Md Toufiqur Rahman: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Apeksha Singh: Institute for Quantitative and Computational Biosciences and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA
Sarina Lowe: Institute for Quantitative and Computational Biosciences and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA
Mohammad Aqdas: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Kevin Jiang: Institute for Quantitative and Computational Biosciences and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA
Haripriya Vaidehi Narayanan: Institute for Quantitative and Computational Biosciences and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA
Alexander Hoffmann: Institute for Quantitative and Computational Biosciences and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA
Myong-Hee Sung: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 3
p. 113940

Abstract

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Summary: Individual cell sensing of external cues has evolved through the temporal patterns in signaling. Since nuclear factor κB (NF-κB) signaling dynamics have been examined using a single subunit, RelA, it remains unclear whether more information might be transmitted via other subunits. Using NF-κB double-knockin reporter mice, we monitored both canonical NF-κB subunits, RelA and c-Rel, simultaneously in single macrophages by quantitative live-cell imaging. We show that signaling features of RelA and c-Rel convey more information about the stimuli than those of either subunit alone. Machine learning is used to predict the ligand identity accurately based on RelA and c-Rel signaling features without considering the co-activated factors. Ligand discrimination is achieved through selective non-redundancy of RelA and c-Rel signaling dynamics, as well as their temporal coordination. These results suggest a potential role of c-Rel in fine-tuning immune responses and highlight the need for approaches that will elucidate the mechanisms regulating NF-κB subunit specificity.

CP: Molecular biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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