Rate thresholds in cell signaling have functional and phenotypic consequences in non-linear time-dependent environments.
Rate thresholds in cell signaling have functional and phenotypic consequences in non-linear time-dependent environments.
复制标题
DOI：
10.3389/fcell.2023.1124874
复制
发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
所有细胞都通过信号转导途径对生理上相关的细胞外细胞因子、应激源、营养水平、激素、形态原和其他刺激做出反应，这些刺激在健康和疾病状态下的浓度和速度不同。细胞信号传递中一个尚未解决的核心基本问题是，除了绝对浓度的差异外，细胞是否以及如何感知和整合细胞外刺激浓度的变化所传达的信息。我们认为，除了不同的信号分子或不同的遗传背景外，随着时间的推移，不同的环境变化还会影响细胞的行为。然而，目前的大多数生物医学研究都集中在剧烈的环境变化上，而没有考虑细胞如何对随时间缓慢变化的环境做出反应。作为这种环境变化的一个例子，我们回顾了细胞对环境速率变化的敏感性，包括速率阈值的新机制。速率阈值被定义为环境中的变化速率的阈值，其中低于阈值的速率值不激活信令，高于阈值的速率值导致信号激活。我们综述了酵母中的p38/Hog1渗透胁迫信号，细菌中的趋化性和应激反应，阿米巴中的环磷酸腺苷信号，哺乳动物细胞中的生长因子信号，发育过程中的形态动力学，葡萄糖和胰岛素信号的时间动态，以及肾脏中的时空应激源。这些文献回顾的例子表明，速率阈值是普遍存在的，而且是细胞信号的一个被低估的基本属性。最后，通过研究非线性环境中的细胞，我们勾勒出在正常和病理生理条件下更好地理解细胞生理学的未来方向。
All cells employ signal transduction pathways to respond to physiologically relevant extracellular cytokines, stressors, nutrient levels, hormones, morphogens, and other stimuli that vary in concentration and rate in healthy and diseased states. A central unsolved fundamental question in cell signaling is whether and how cells sense and integrate information conveyed by changes in the rate of extracellular stimuli concentrations, in addition to the absolute difference in concentration. We propose that different environmental changes over time influence cell behavior in addition to different signaling molecules or different genetic backgrounds. However, most current biomedical research focuses on acute environmental changes and does not consider how cells respond to environments that change slowly over time. As an example of such environmental change, we review cell sensitivity to environmental rate changes, including the novel mechanism of rate threshold. A rate threshold is defined as a threshold in the rate of change in the environment in which a rate value below the threshold does not activate signaling and a rate value above the threshold leads to signal activation. We reviewed p38/Hog1 osmotic stress signaling in yeast, chemotaxis and stress response in bacteria, cyclic adenosine monophosphate signaling in Amoebae, growth factors signaling in mammalian cells, morphogen dynamics during development, temporal dynamics of glucose and insulin signaling, and spatio-temproral stressors in the kidney. These reviewed examples from the literature indicate that rate thresholds are widespread and an underappreciated fundamental property of cell signaling. Finally, by studying cells in non-linear environments, we outline future directions to understand cell physiology better in normal and pathophysiological conditions.
登录
查看更多内容
影响因子：
8
作者：
Artemenko, Yulia;Lampert, Thomas J.;Devreotes, Peter N.
通讯作者：
Devreotes, Peter N.
影响因子：
7.7
作者：
BRATUSCHMARRAIN, PR;KOMJATI, M;WALDHAUSL, WK
通讯作者：
WALDHAUSL, WK
影响因子：
7.3
作者：
Fujita, Kazuhiro A.;Toyoshima, Yu;Kuroda, Shinya
通讯作者：
Kuroda, Shinya
DOI：
10.2215/cjn.08750812
发表时间：
2014-10-01
影响因子：
9.8
作者：
Dantzler, William H.;Layton, Anita T.;Pannabecker, Thomas L.
通讯作者：
Pannabecker, Thomas L.
影响因子：
5.8
作者：
Jashnsaz H;Fox ZR;Hughes JJ;Li G;Munsky B;Neuert G
通讯作者：
Neuert G