A myriad of inflammatory cytokines regulate signaling pathways to maintain cellular homeostasis. The IkB kinase (IKK) complex is an integration hub for cytokines that govern nuclear factor kB (NF-kB) 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. In this paper, the Lee Lab track dynamics of IKK complexes and nuclear NF-kB to identify upstream signaling features that determine same-cell responses. Experiments and modeling of single complexes reveal their size, number, and timing relays cytokine-specific control over shared signaling mechanisms with feedback regulation that is independent of transcription. Their results provide evidence for variable-gain stochastic pooling, a noise-reducing motif that enables cytokine-specific regulation and parsimonious information transfer. They propose that emergent properties of stochastic pooling are general principles of receptor signaling that have evolved for constructive information transmission in noisy molecular environments.
Cruz JA*, Mokashi CS*, Kowalczyk GJ, Guo Y, Zhang Q, Gupta S, Schipper DL, Smeal SW, Lee REC. A variable-gain stochastic pooling motif mediates information transfer from receptor assemblies into NF-kB. Sci. Adv. 7, eabi9410 (2021)