A stochastic pooling motif mediates information transfer from receptor assemblies into NF-κB

Cruz, J. A.; Mokashi, C. S.; Kowalczyk, G. J.; Guo, Y.; Zhang, Q.; Gupta, S.; Schipper, D. L.; Lee, R. E. C.

doi:10.1101/2021.03.29.437543

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bioRxiv · 10.1101/2021.03.29.437543

A stochastic pooling motif mediates information transfer from receptor assemblies into NF-κB

Cruz, J. A.·Mokashi, C. S.·Kowalczyk, G. J.·Guo, Y.·Zhang, Q.·Gupta, S.·Schipper, D. L.·Lee, R. E. C.

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Abstract

A myriad of inflammatory cytokines regulate signaling pathways to maintain cellular homeostasis. The IKK complex is an integration hub for cytokines that govern NF-{kappa}B signaling. In response to inflammation, IKK is activated through recruitment to receptor-associated protein assemblies. How and what information IKK complexes transmit about the milieu are open questions. Here we track dynamics of IKK complexes and nuclear NF-{kappa}B to identify upstream signaling features that determine same-cell responses. Experiments and modeling of single complexes reveals their size, number, and timing relays cytokine-specific information with feedback control that is independent of transcription. Our results provide evidence for variable-gain stochastic pooling, a noise-reducing motif that enables parsimonious and cytokine-specific information transfer. We propose that emergent properties of stochastic pooling are general principles of receptor signaling. One Sentence SummaryA variable-gain stochastic pooling motif mediates robust and tunable information transmission from the extracellular milieu into the cell.

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Cruz, J. A., Mokashi, C. S., Kowalczyk, G. J., Guo, Y., Zhang, Q., Gupta, S., Schipper, D. L., Lee, R. E. C.. 2021-03-30. A stochastic pooling motif mediates information transfer from receptor assemblies into NF-κB. https://doi.org/10.1101/2021.03.29.437543

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