Open AccessA variable-gain stochastic pooling motif mediates information transfer from receptor assemblies into NF-κB
Author(s) -
J. Agustin Cruz,
Chaitanya Mokashi,
Gabriel J. Kowalczyk,
Yue Guo,
Liqun Zhang,
Sheena Gupta,
David L. Schipper,
Steven W. Smeal,
Robin Lee
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abi9410
Subject(s) - pooling , motif (music) , information transmission , computational biology , extracellular , biology , computer science , microbiology and biotechnology , artificial intelligence , physics , computer network , acoustics
A myriad of inflammatory cytokines regulate signaling pathways to maintain cellular homeostasis. The IκB kinase (IKK) complex is an integration hub for cytokines that govern nuclear factor κB (NF-κB) 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-κB 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. Our results provide evidence for variable-gain stochastic pooling, a noise-reducing motif that enables cytokine-specific regulation and parsimonious information transfer. We propose that emergent properties of stochastic pooling are general principles of receptor signaling that have evolved for constructive information transmission in noisy molecular environments.