Information Transfer via Gonadotropin-Releasing Hormone Receptors to ERK and NFAT: Sensing GnRH and Sensing Dynamics.
Information Transfer via Gonadotropin-Releasing Hormone Receptors to ERK and NFAT: Sensing GnRH and Sensing Dynamics.
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DOI：
10.1210/js.2016-1096
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发表时间：
2017-04-01
影响因子：
4.1
通讯作者：
McArdle CA
中科院分区：
文献类型：
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作者：
Garner KL;Voliotis M;Alobaid H;Perrett RM;Pham T;Tsaneva-Atanasova K;McArdle CA
信息论方法可以用来量化通过细胞信令网络进行的信息传递。在这项研究中，我们在大量固定的LβT2和HeLa细胞中，通过促性腺激素释放激素激活细胞外信号调节激酶和活化T细胞的核因子。通过GnRH和ERK或NFAT之间的互信息衡量的信息传输为1位(尽管系统输入为3位)。检测ERK和NFAT均可使其升高，但增加幅度为50%。在活细胞中，通过GnRH受体向NFAT传递的信息也增加了1比特，并考虑到反应轨迹而增加，但增加了10%。GnRH的分泌是脉动的，所以我们探索了通过感知第二个脉冲获得的信息，开发了一个GnRH信号到NFAT的模型，通过允许效应器的波动引入了变异性。模拟显示，当细胞-细胞变异性反映快速波动的效应器水平时，通过检测两个GnRH脉冲获得额外信息，但如果是由于缓慢波动的效应器，一个脉冲中的反应是对另一个脉冲中的反应的预测，因此从检测两个脉冲中获得的信息很少。湿实验室实验表明，后一种情况适用于GnRH信号；在我们的实验时间范围内(1至2小时)，NFAT途径中的细胞间可变性保持相对恒定，因此轨迹可在脉冲之间重现。因此，联合感知、反应轨迹感知和重复脉冲感知都可以增加通过GnRH受体的信息传递，但在每种情况下增加的幅度都很小。通过联合感知ERK和NFAT以及感知轨迹，GnRHR的信息传递增加，但增加的幅度很小，因为大多数信息是通过这些嘈杂的信号通路丢失的。
Information theoretic approaches can be used to quantify information transfer via cell signaling networks. In this study, we do so for gonadotropin-releasing hormone (GnRH) activation of extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) in large numbers of individual fixed LβT2 and HeLa cells. Information transfer, measured by mutual information between GnRH and ERK or NFAT, was <1 bit (despite 3-bit system inputs). It was increased by sensing both ERK and NFAT, but the increase was <50%. In live cells, information transfer via GnRH receptors to NFAT was also <1 bit and was increased by consideration of response trajectory, but the increase was <10%. GnRH secretion is pulsatile, so we explored information gained by sensing a second pulse, developing a model of GnRH signaling to NFAT with variability introduced by allowing effectors to fluctuate. Simulations revealed that when cell–cell variability reflects rapidly fluctuating effector levels, additional information is gained by sensing two GnRH pulses, but where it is due to slowly fluctuating effectors, responses in one pulse are predictive of those in another, so little information is gained from sensing both. Wet laboratory experiments revealed that the latter scenario holds true for GnRH signaling; within the timescale of our experiments (1 to 2 hours), cell–cell variability in the NFAT pathway remains relatively constant, so trajectories are reproducible from pulse to pulse. Accordingly, joint sensing, sensing of response trajectories, and sensing of repeated pulses can all increase information transfer via GnRH receptors, but in each case the increase is small. Information transfer via GnRHR is increased by joint sensing of ERK and NFAT and by sensing trajectories, but the increases are small, as most information is lost through these noisy signaling pathways.