Coupling of cell energetics with membrane metabolic sensing - Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out
Coupling of cell energetics with membrane metabolic sensing - Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out
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DOI：
10.1074/jbc.m201777200
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发表时间：
2002-07-05
影响因子：
4.8
通讯作者：
Terzic, A
中科院分区：
文献类型：
--
作者：
Abraham, MR;Selivanov, VA;Terzic, A
代谢信号的转导在维持细胞内稳态中是必不可少的。然而，管理膜代谢传感器与细胞代谢的整合和同步的原理仍然难以捉摸。在这里，细胞的核苷酸通量和ATP敏感的K+（K-ATP）通道，原型代谢传感器的核苷酸依赖性门控的分析，揭示了一个扩散屏障内的亚膜空间，阻止直接接收胞质信号。肌酸激酶磷酸转移，捕获O-18-辅助P-31 NMR，密切配合ATP营业额，反映了细胞的能量状态。通过肌酸激酶中继的高能量磷酰基转移的动力学允许将高能信号高保真地传输到膜下室中，使K-ATP通道活性与细胞代谢同步。肌酸激酶M-CK基因的敲除破坏了K-ATP通道的信号传递，并产生了具有增加的电脆弱性的细胞表型。因此，在区室化的细胞环境中，磷酸转移系统分流扩散障碍，并将代谢传感器与细胞能量网络整合在一起。
Transduction of metabolic signals is essential in preserving cellular homeostasis. Yet, principles governing integration and synchronization of membrane metabolic sensors with cell metabolism remain elusive. Here, analysis of cellular nucleotide fluxes and nucleotide-dependent gating of the ATP-sensitive K+ (K-ATP) channel, a prototypic metabolic sensor, revealed a diffusional barrier within the submembrane space, preventing direct reception of cytosolic signals. Creatine kinase phosphotransfer, captured by O-18-assisted P-31 NMR, coordinated tightly with ATP turnover, reflecting the cellular energetic status. The dynamics of high energy phosphoryl transfer through the creatine kinase relay permitted a high fidelity transmission of energetic signals into the submembrane compartment synchronizing K-ATP channel activity with cell metabolism. Knock-out of the creatine kinase M-CK gene disrupted signal delivery to K-ATP channels and generated a cellular phenotype with increased electrical vulnerability. Thus, in the compartmentalized cell environment, phosphotransfer systems shunt diffusional barriers and secure regimented signal transduction integrating metabolic sensors with the cellular energetic network.