A variable-gain stochastic pooling motif mediates information transfer from receptor assemblies into NF-κB.
A variable-gain stochastic pooling motif mediates information transfer from receptor assemblies into NF-κB.
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DOI：
10.1126/sciadv.abi9410
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发表时间：
2021-07
期刊：
影响因子：
13.6
通讯作者：
Lee REC
中科院分区：
文献类型：
--
作者：
Cruz JA;Mokashi CS;Kowalczyk GJ;Guo Y;Zhang Q;Gupta S;Schipper DL;Smeal SW;Lee REC
一个可变增益随机池基序介导的强大和吝啬的信息传输从细胞外环境。无数的炎性细胞因子调节信号通路以维持细胞内稳态。IκB激酶（IKK）复合物是控制核因子κB（NF-κB）信号传导的细胞因子的整合中心。在炎症反应中，IKK通过募集受体相关蛋白组装体而被激活。IKK复合体如何以及传递什么样的环境信息是一个悬而未决的问题。在这里，我们跟踪IKK复合物和核NF-κB的动力学，以确定上游信号特征，确定相同的细胞反应。单个复合物的实验和建模揭示了它们的大小、数量和时间继电器对共享信号传导机制的特定控制，其具有独立于转录的反馈调节。我们的研究结果为可变增益随机池提供了证据，可变增益随机池是一种降噪基序，可以实现特定的生物调节和简约的信息传递。我们建议，紧急性质的随机汇集的一般原则，已演变为建设性的信息传输在嘈杂的分子环境中的受体信号。
A variable-gain stochastic pooling motif mediates robust and parsimonious information transmission from the extracellular milieu. 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.
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