Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations.
Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations.
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激素诱导的钙振荡取决于与肌醇1,4,5-三磷酸的交叉偶联。
DOI：
10.1016/j.celrep.2014.10.033
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发表时间：
2014-11-20
期刊：
影响因子：
8.8
通讯作者：
Thomas AP
中科院分区：
文献类型：
--
作者：
Gaspers LD;Bartlett PJ;Politi A;Burnett P;Metzger W;Johnston J;Joseph SK;Höfer T;Thomas AP
受体介导的胞浆Ca ~（2+）浓度振荡（[Ca ~（2+）]i）可能直接来源于肌醇1，4，5-三磷酸（IP 3）受体上的自主Ca ~（2+）反馈振荡器，也可能是IP 3代谢上的Ca ~（2+）反馈驱动的IP 3振荡的继发结果。区分这些替代方案具有挑战性，因为IP 3波动可能驱动Ca 2+振荡，或者可能只是对[Ca 2 +]i尖峰的二次响应。为了研究这个问题，我们构建了一个重组IP 3缓冲液使用I型IP 3受体配体结合域融合到绿色荧光蛋白（GFP-LBD），缓冲IP 3在生理范围内。该IP 3缓冲器减缓了微扰诱导的[IP 3]动力学，而不改变稳态[IP 3]。GFP-LBD以剂量依赖性方式干扰[Ca 2 +]i振荡：它降低[Ca 2 +]i上升速率和Ca 2+波传播速度，并且在高水平下完全消除[Ca 2 +]i振荡。这些数据，连同计算建模，表明IP 3动力学在产生[Ca 2 +]i振荡和波中起着重要作用。Gaspers等人使用基因编码的IP 3缓冲液来抑制激素刺激期间的IP 3动力学。使用这种方法，他们发现Ca 2+对IP 3形成的正反馈是一个重要组成部分，产生长周期的基线分离的Ca 2+振荡和细胞内Ca 2+波。
Receptor-mediated oscillations in cytosolic Ca2+ concentration ([Ca2+]i) could originate either directly from an autonomous Ca2+ feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca2+ feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca2+ oscillations or could just be a secondary response to the [Ca2+]i spikes. To investigate this problem, we constructed a recombinant IP3 buffer using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range. This IP3 buffer slows hormone-induced [IP3] dynamics without changing steady-state [IP3]. GFP-LBD perturbed [Ca2+]i oscillations in a dose-dependent manner: it decreased both the rate of [Ca2+]i rise and the speed of Ca2+ wave propagation and, at high levels, abolished [Ca2+]i oscillations completely. These data, together with computational modeling, demonstrate that IP3 dynamics play a fundamental role in generating [Ca2+]i oscillations and waves. Gaspers et al. use a genetically encoded IP3 buffer to suppress IP3 dynamics during hormonal stimulation. Using this approach, they find that positive feedback of Ca2+ on IP3 formation is an essential component, generating long-period, baseline-separated Ca2+ oscillations and intracellular Ca2+ waves.
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DOI：
10.1073/pnas.89.20.9895
发表时间：
1992-10-15
影响因子：
11.1
作者：
DEYOUNG, GW;KEIZER, J
通讯作者：
KEIZER, J
影响因子：
11.4
作者：
Hajnoczky, G;Thomas, AP
通讯作者：
Thomas, AP
影响因子：
3.3
作者：
KEIZER, J;LI, YX;RINZEL, J
通讯作者：
RINZEL, J
影响因子：
11.4
作者：
OSIPCHUK, YV;WAKUI, M;PETERSEN, OH
通讯作者：
PETERSEN, OH
影响因子：
7.8
作者：
Várnai, P;Balla, T
通讯作者：
Balla, T