Posttranslational modifications of cardiac ryanodine receptors: Ca(2+) signaling and EC-coupling.
Posttranslational modifications of cardiac ryanodine receptors: Ca(2+) signaling and EC-coupling.
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DOI：
10.1016/j.bbamcr.2012.08.016
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发表时间：
2013-04
影响因子：
5.1
通讯作者：
Shirokova, Natalia
中科院分区：
文献类型：
--
作者：
Niggli, Ernst;Ullrich, Nina D.;Gutierrez, Daniel;Kyrychenko, Sergii;Polakova, Eva;Shirokova, Natalia
在心肌中，一些翻译后的蛋白质修饰可以改变肌浆网(SR)的钙释放通道的功能，也被称为兰尼定受体(RyR)。在每一次心跳中，RyRs被钙离子诱导的钙释放机制激活，并贡献了收缩所需的很大一部分钙离子。已知RyR的一些翻译后修饰会影响其门控和钙敏感性。目前，许多实验室的研究集中在由PKA和CaMKII引起的RyR磷酸化，或由活性氧和氮物种(ROS/RNS)引起的RyR修饰。这两类翻译后修饰被认为在通道活动的生理调节中发挥重要作用，但也被认为在各种疾病中引起异常改变。直到最近，人们才意识到几种类型的翻译后修饰紧密相连，形成协同(或拮抗)反馈环，从而产生相加的和潜在的有害下游影响。这篇综述总结了最近关于这种翻译后修饰的发现，试图将分子和细胞的发现联系起来，并为未来的工作打开了一个视角，试图理解串扰在这些多个信号通路中的影响。澄清这些复杂的相互作用对开发新的治疗方法将是重要的，因为这可能为未来实施多管齐下的治疗制度奠定基础。
In cardiac muscle, a number of posttranslational protein modifications can alter the function of the Ca2+ release channel of the sarcoplasmic reticulum (SR), also known as the ryanodine receptor (RyR). During every heartbeat RyRs are activated by the Ca2+-induced Ca2+ release mechanism and contribute a large fraction of the Ca2+ required for contraction. Some of the posttranslational modifications of the RyR are known to affect its gating and Ca2+ sensitivity. Presently, research in a number of laboratories is focussed on RyR phosphorylation, both by PKA and CaMKII, or on RyR modifications caused by reactive oxygen and nitrogen species (ROS / RNS). Both classes of posttranslational modifications are thought to play important roles in the physiological regulation of channel activity, but are also known to provoke abnormal alterations during various diseases. Only recently it was realized that several types of posttranslational modifications are tightly connected and form synergistic (or antagonistic) feed-back loops resulting in additive and potentially detrimental downstream effects. This review summarizes recent findings on such posttranslational modifications, attempts to bridge molecular with cellular findings, and opens a perspective for future work trying to understand the ramifications of crosstalk in these multiple signaling pathways. Clarifying these complex interactions will be important in the development of novel therapeutic approaches, since this may form the foundation for the implementation of multi-pronged treatment regimes in the future.
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DOI：
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发表时间：
2003-06-01
影响因子：
3.5
作者：
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作者：
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影响因子：
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