巨细胞在对连接物混合物的反应中保持信号忠诚度
bioRxiv : the preprint server for biology
|April 16, 2025
概括
巨细胞保持刺激-反应特异性 (SRS),即使有多个免疫信号. 数学建模和实验表明,它们的NFκB信号代码能够强大区分威胁,确保适当的免疫反应.
科学领域:
- 免疫学和计算生物学
- 细胞信号的动力学
- 系统生物学 系统生物学
背景情况:
- 巨细胞作为免疫哨兵,需要对各种威胁作出特定的反应.
- 核因子kappa B (NFκB) 信号动态编码刺激-反应特异性 (SRS).
- 生理条件涉及复杂的多连接体暴露,与简化的实验设置不同.
研究的目的:
- 研究巨细胞如何整合多连接体信息,并在复杂条件下维持SRS.
- 使用数学模型系统地模拟和分析NFκB对组合联体混合物的反应.
- 用活细胞显微镜验证模型预测,并根据实验差异改进模型.
主要方法:
- 利用已确立的异质单细胞NFκB反应的数学模型.
- 执行了对多达五个配体混合物的巨细胞反应的系统模拟.
- 用活细胞显微镜验证模型预测,改进模型以考虑内体体运输限制和带对抗性.
主要成果:
- 该模型成功预测了对多连接体混合物的反应,揭示了TLR3和TLR9连接体之间的对抗性,这是由于内体体运输的限制.
- 在所有组合性连接物条件中,系统地分析了刺激-反应特异性 (SRS).
- 巨细胞最有效地区分单连接体刺激,随着连接体数量的增加,区分能力下降,但仍然保持统计学意义.
结论:
- 巨体表现出强大的NFκB时间信号代码,即使在复杂的多连接体环境中,也能够对免疫威胁进行分类.
- 这项研究揭示了先前未被赞赏的先天免疫反应特异性的强度.
- 研究结果强调NFκB动态能够保持刺激-反应特异性,确保适当的免疫反应.
相关概念视频
Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
Diversity in Cell Signaling Responses
6.3K
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
6.3K
Signal Transduction: Overview
8.1K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
8.1K
Overview of Cell Signaling
19.8K
Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate with the environment.
Cells respond to many types of information, often through receptor proteins positioned on the membrane. For example, skin cells respond to and transmit touch...
Cells respond to many types of information, often through receptor proteins positioned on the membrane. For example, skin cells respond to and transmit touch...
19.8K
Amplifying Signals via Enzymatic Cascade
8.2K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.2K
Assembly of Signaling Complexes
5.6K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.6K


