Dendritic geometry shapes neuronal cAMP signalling to the nucleus.
Dendritic geometry shapes neuronal cAMP signalling to the nucleus.
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DOI：
10.1038/ncomms7319
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发表时间：
2015-02-18
影响因子：
16.6
通讯作者：
Girault, Jean-Antoine
中科院分区：
文献类型：
--
作者：
Li, Lu;Gervasi, Nicolas;Girault, Jean-Antoine
神经元有复杂的树突树，从不同距离的细胞体接收大量的输入。然而分子信号从树突到细胞核的传播规律尚不清楚。DARPP-32是纹状体输出神经元中磷酸化调控的信号中枢。我们结合扩散反应模型和实时成像来研究camp激活的DARPP-32向细胞核的信号传导。该模型预测，由于枝晶直径的节段性减小，对次生枝晶cAMP生成核的影响最大。分支、核周大小或棘的变化没有那么明显的影响。cAMP或多巴胺释放后的生物传感器激酶活性测量证实了这些预测。受这一途径调控的组蛋白3磷酸化，在二级样树突中释放的cAMP最能刺激组蛋白3磷酸化。因此，出乎意料的是，基于扩散的信号从树突到细胞核的有效性并不与距离成反比。我们提出了一种一般机制，通过这种机制，树突的几何形状抵消了树突距离对细胞核信号传递的影响。神经元有复杂的树突树，但控制信号从树突到细胞核传播的规则尚不清楚。在这里，作者结合扩散反应模型和实时成像来研究神经元中cAMP信号的调节机制，并发现树突状树的几何形状决定了突触到细胞核的信号传导。
Neurons have complex dendritic trees, receiving numerous inputs at various distances from the cell body. Yet the rules of molecular signal propagation from dendrites to nuclei are unknown. DARPP-32 is a phosphorylation-regulated signalling hub in striatal output neurons. We combine diffusion-reaction modelling and live imaging to investigate cAMP-activated DARPP-32 signalling to the nucleus. The model predicts maximal effects on the nucleus of cAMP production in secondary dendrites, due to segmental decrease of dendrite diameter. Variations in branching, perikaryon size or spines have less pronounced effects. Biosensor kinase activity measurement following cAMP or dopamine uncaging confirms these predictions. Histone 3 phosphorylation, regulated by this pathway, is best stimulated by cAMP released in secondary-like dendrites. Thus, unexpectedly, the efficacy of diffusion-based signalling from dendrites to nucleus is not inversely proportional to the distance. We suggest a general mechanism by which dendritic geometry counterbalances the effect of dendritic distance for signalling to the nucleus. Neurons have complex dendritic trees but the rules governing the propagation of signals from dendrites to nuclei remain unclear. Here the authors combine diffusion-reaction modelling and live imaging to investigate the mechanisms regulating cAMP signalling in neurons and find that dendritic tree geometry shapes synapse-to-nucleus signalling.
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影响因子：
4.3
作者：
Fernandez E;Schiappa R;Girault JA;Le Novère N
通讯作者：
Le Novère N
影响因子：
2.5
作者：
Hoffman, DA;Johnston, D
通讯作者：
Johnston, D
影响因子：
3.8
作者：
Fisher, Wayne G.;Yang, Pei-Chi;Medikonduri, Ram K.;Jafri, M. Saleet
通讯作者：
Jafri, M. Saleet
影响因子：
--
作者：
Cowan, Ann E.;Moraru, Ion I.;Schaff, James C.;Slepchenko, Boris M.;Loew, Leslie M.
通讯作者：
Loew, Leslie M.
影响因子：
3.4
作者：
GOLDSTEIN, SS;RALL, W
通讯作者：
RALL, W