Evolutionary and functional perspectives on signaling from neuronal surface to nucleus.
Evolutionary and functional perspectives on signaling from neuronal surface to nucleus.
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DOI：
10.1016/j.bbrc.2015.02.146
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发表时间：
2015-04-24
影响因子：
3.1
通讯作者：
Ma H
中科院分区：
文献类型：
--
作者：
Cohen SM;Li B;Tsien RW;Ma H
在进化过程中，对钙信号的依赖一直被很好地保存下来。虽然钙信号通路的复杂性已经增加，但包括CREB在内的转录因子被钙/钙调素依赖的激酶(CaMKs)激活仍然是长期可塑性的关键。在线虫中，CaMK家族只由三个成员组成，而CREB的磷酸化是由CaMKI的同源物CMK-1介导的。CMK-1核易位直接调节趋热行为对环境变化的适应。在哺乳动物中，CaMK家族已经从三个成员扩大到十个成员，使得信号转导途径的单个元件能够专门化，并增加了对CaMKII亚家族的依赖。这种增加的复杂性使得细胞表面的钙源和特定的细胞靶点之间能够进行专线通信。利用新的和以前发表的数据，我们回顾了γCaMKII-CaM核易位的机制。这种错综复杂的途径依赖于多种钙/钙调素依赖的激酶和磷酸酶的特定作用：α/βCaMKII磷酸化γCaMKII以捕获CaM；Can去磷酸化γCaMKII，将其调度到细胞核；以及PP2A诱导γCaMKII释放CaM，使CaMKK和CaMKIV触发CREB磷酸化。因此，虽然线虫的某些基本元件被保留下来，但进化修改提供了有针对性的交流、关键节点和检查点的调节以及信号转导的更大特异性和灵活性的机会。
Reliance on Ca2+ signaling has been well-preserved through the course of evolution. While the complexity of Ca2+ signaling pathways has increased, activation of transcription factors including CREB by Ca2+/CaM-dependent kinases (CaMKs) has remained critical for long-term plasticity. In C. elegans, the CaMK family is made up of only three members, and CREB phosphorylation is mediated by CMK-1, the homologue of CaMKI. CMK-1 nuclear translocation directly regulates adaptation of thermotaxis behavior in response to changes in the environment. In mammals, the CaMK family has been expanded from three to ten members, enabling specialization of individual elements of a signal transduction pathway and increased reliance on the CaMKII subfamily. This increased complexity enables private line communication between Ca2+ sources at the cell surface and specific cellular targets. Using both new and previously published data, we review the mechanism of a γCaMKII-CaM nuclear translocation. This intricate pathway depends on a specific role for multiple Ca2+/CaM-dependent kinases and phosphatases: α/βCaMKII phosphorylates γCaMKII to trap CaM; CaN dephosphorylates γCaMKII to dispatch it to the nucleus; and PP2A induces CaM release from γCaMKII so that CaMKK and CaMKIV can trigger CREB phosphorylation. Thus, while certain basic elements have been conserved from C. elegans, evolutionary modifications offer opportunities for targeted communication, regulation of key nodes and checkpoints, and greater specificity and flexibility in signaling.