Friedrich-Miescher Institute for Biomedical Research, Department of Neurobiology, Maulbeerstr. 66, 4058 Basel, Switzerland.
Cell Calcium. 2011 May;49(5):296-305. doi: 10.1016/j.ceca.2010.11.009. Epub 2010 Dec 15.
Activity-dependent gene expression is important for the formation and maturation of neuronal networks, neuronal survival and for plastic modifications within mature networks. At the level of individual neurons, expression of new protein is required for dendritic branching, synapse formation and elimination. Experience-driven synaptic activity induces membrane depolarization, which in turn evokes intracellular calcium transients that are decoded according to their source and strength by intracellular calcium sensing proteins. In order to activate the gene transcription machinery of the cell, calcium signals have to be conveyed from the site of their generation in the cytoplasm to the cell nucleus. This can occur via a variety of mechanisms and with different kinetics depending on the source and amplitude of calcium influx. One mechanism involves the propagation of calcium itself, leading to nuclear calcium transients that subsequently activate transcription. The mitogen-activated protein kinase (MAPK) cascade represents a second central signaling module that transduces information from the site of calcium signal generation at the plasma membrane to the nucleus. Nuclear signaling of the MAPK cascades catalyzes the phosphorylation of transcription factors but also regulates gene transcription more globally at the level of chromatin remodeling as well as through its recently identified role in the modulation of nuclear shape. Here we discuss the possible mechanisms by which the MAPKs ERK1 and ERK2, activated by synaptically evoked calcium influx, can signal to the nucleus and regulate gene transcription. Moreover, we describe how MAPK-dependent structural plasticity of the nuclear envelope enhances nuclear calcium signaling and suggest possible implications for the regulation of gene transcription in the context of nuclear geometry.
活性依赖性基因表达对于神经元网络的形成和成熟、神经元存活以及成熟网络中的可塑性修饰非常重要。在单个神经元水平上，新蛋白质的表达对于树突分支、突触形成和消除是必需的。经验驱动的突触活动诱导膜去极化，进而引发细胞内钙瞬变，这些钙瞬变根据其来源和强度被细胞内钙感应蛋白解码。为了激活细胞的基因转录机制，钙信号必须从细胞质中产生的部位传递到细胞核。这可以通过多种机制发生，并且取决于钙流入的来源和幅度，具有不同的动力学。一种机制涉及钙本身的传播，导致随后激活转录的核钙瞬变。丝裂原活化蛋白激酶 (MAPK) 级联反应代表了从质膜上钙信号产生部位向细胞核传递信息的第二个核心信号模块。MAPK 级联的核信号转导催化转录因子的磷酸化，但也通过染色质重塑以及其在核形状调节中的新发现作用在更全局的水平上调节基因转录。在这里，我们讨论了由突触诱发的钙流入激活的 MAPK（ERK1 和 ERK2）向核内信号转导并调节基因转录的可能机制。此外，我们描述了核膜中 MAPK 依赖性结构可塑性如何增强核钙信号转导，并提出了在核几何形状背景下调节基因转录的可能意义。
