Nuclear BK channels regulate gene expression via the control of nuclear calcium signaling.

Nuclear BK channels regulate gene expression via the control of nuclear calcium signaling.
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核 BK 通道通过控制核钙信号传导来调节基因表达。

DOI:
10.1038/nn.3744
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发表时间:
2014-08
影响因子:
25
通讯作者:
Gao, Tian-Ming
Gao, Tian-Ming
中科院分区:
医学1区
文献类型:
--
作者:
Li, Boxing;Jie, Wei;Huang, Lianyan;Wei, Peng;Li, Shuji;Luo, Zhengyi;Friedman, Allyson K.;Meredith, Andrea L.;Han, Ming-Hu;Zhu, Xin-Hong;Gao, Tian-Ming

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离子通道对于调节神经元功能是必不可少的。质膜、线粒体、内质网和溶酶体离子通道在Ca 2+调节中的重要性已得到充分证实。相比之下,令人惊讶的是,对核被膜(NE)上离子通道的功能知之甚少。在这里,我们证明了功能性大电导,钙激活钾通道(BK通道)的啮齿动物海马神经元的NE的存在。核BK通道(nBK通道)的功能性阻断诱导NE源性Ca 2+释放、核质Ca 2+升高和cAMP反应元件结合蛋白(CREB)依赖性转录。更重要的是,阻断nBK通道调节核Ca 2+敏感基因的表达,并以核Ca 2+依赖的方式促进树突状分支。这些结果表明,nBK通道作为神经元活动和核Ca ~(2+)之间的分子连接器,将信号从突触传递到核,是NE水平上突触活动依赖性神经元功能的新调节剂。
Ion channels are essential for the regulation of neuronal functions. The significance of plasma membrane, mitochondrial, endoplasmic reticulum, and lysosomal ion channels in the regulation of Ca2+ is well established. In contrast, surprisingly less is known about the function of ion channels on the nuclear envelope (NE). Here we demonstrate the presence of functional large-conductance, calcium-activated potassium channels (BK channels) on the NE of rodent hippocampal neurons. Functionally blockade of nuclear BK channels (nBK channels) induces NE-derived Ca2+ release, nucleoplasmic Ca2+ elevation, and cAMP response element binding protein (CREB)-dependent transcription. More importantly, blockade of nBK channels regulates nuclear Ca2+-sensitive gene expression and promotes dendritic arborization in a nuclear Ca2+-dependent manner. These results suggest that nBK channel functions as a molecular linker between neuronal activity and nuclear Ca2+ to convey the signals from synapse to nucleus and is a new modulator for synaptic activity-dependent neuronal functions at the NE level.
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