Carrasco A J, Dzeja P P, Alekseev A E, Pucar D, Zingman L V, Abraham M R, Hodgson D, Bienengraeber M, Puceat M, Janssen E, Wieringa B, Terzic A
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Mayo Foundation, Guggenheim 7, 200 First Street Southwest, Rochester, MN 55905, USA.
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7623-8. doi: 10.1073/pnas.121038198. Epub 2001 Jun 5.
Transduction of energetic signals into membrane electrical events governs vital cellular functions, ranging from hormone secretion and cytoprotection to appetite control and hair growth. Central to the regulation of such diverse cellular processes are the metabolism sensing ATP-sensitive K+ (K(ATP)) channels. However, the mechanism that communicates metabolic signals and integrates cellular energetics with K(ATP) channel-dependent membrane excitability remains elusive. Here, we identify that the response of K(ATP) channels to metabolic challenge is regulated by adenylate kinase phosphotransfer. Adenylate kinase associates with the K(ATP) channel complex, anchoring cellular phosphotransfer networks and facilitating delivery of mitochondrial signals to the membrane environment. Deletion of the adenylate kinase gene compromised nucleotide exchange at the channel site and impeded communication between mitochondria and K(ATP) channels, rendering cellular metabolic sensing defective. Assigning a signal processing role to adenylate kinase identifies a phosphorelay mechanism essential for efficient coupling of cellular energetics with K(ATP) channels and associated functions.
将能量信号转导为膜电活动，控制着从激素分泌、细胞保护到食欲控制和毛发生长等重要的细胞功能。对如此多样的细胞过程进行调节的核心是代谢感应ATP敏感性钾离子（K(ATP)）通道。然而，将代谢信号与细胞能量学与依赖K(ATP)通道的膜兴奋性相整合的机制仍然难以捉摸。在这里，我们发现K(ATP)通道对代谢挑战的反应是由腺苷酸激酶磷酸转移调节的。腺苷酸激酶与K(ATP)通道复合物结合，锚定细胞磷酸转移网络，并促进线粒体信号传递到膜环境。删除腺苷酸激酶基因会损害通道位点的核苷酸交换，并阻碍线粒体与K(ATP)通道之间的通讯，导致细胞代谢感应缺陷。赋予腺苷酸激酶信号处理作用，确定了一种磷中继机制，这对于细胞能量学与K(ATP)通道及相关功能的有效偶联至关重要。
