Antunes Gabriela, Roque Antonio C, Simoes de Souza Fabio M
Laboratory of Neural Systems (SisNe), Department of Physics, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Center for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo, SP, Brasil.
Sci Rep. 2016 Apr 1;6:23730. doi: 10.1038/srep23730.
Frequently, a common chemical entity triggers opposite cellular processes, which implies that the components of signalling networks must detect signals not only through their chemical natures, but also through their dynamic properties. To gain insights on the mechanisms of discrimination of the dynamic properties of cellular signals, we developed a computational stochastic model and investigated how three calcium ion (Ca(2+))-dependent enzymes (adenylyl cyclase (AC), phosphodiesterase 1 (PDE1), and calcineurin (CaN)) differentially detect Ca(2+) transients in a hippocampal dendritic spine. The balance among AC, PDE1 and CaN might determine the occurrence of opposite Ca(2+)-induced forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD). CaN is essential for LTD. AC and PDE1 regulate, indirectly, protein kinase A, which counteracts CaN during LTP. Stimulations of AC, PDE1 and CaN with artificial and physiological Ca(2+) signals demonstrated that AC and CaN have Ca(2+) requirements modulated dynamically by different properties of the signals used to stimulate them, because their interactions with Ca(2+) often occur under kinetic control. Contrarily, PDE1 responds to the immediate amplitude of different Ca(2+) transients and usually with the same Ca(2+) requirements observed under steady state. Therefore, AC, PDE1 and CaN decode different dynamic properties of Ca(2+) signals.
通常情况下，一种常见的化学实体可触发相反的细胞过程，这意味着信号网络的组成部分不仅必须通过其化学性质，还需通过其动态特性来检测信号。为深入了解细胞信号动态特性的辨别机制，我们开发了一种计算随机模型，并研究了三种钙离子（Ca(2+)）依赖性酶（腺苷酸环化酶（AC）、磷酸二酯酶1（PDE1）和钙调神经磷酸酶（CaN））如何在海马树突棘中差异检测Ca(2+)瞬变。AC、PDE1和CaN之间的平衡可能决定相反的Ca(2+)诱导形式的突触可塑性、长时程增强（LTP）和长时程抑制（LTD）的发生。CaN对LTD至关重要。AC和PDE1间接调节蛋白激酶A，后者在LTP期间对抗CaN。用人造和生理Ca(2+)信号刺激AC、PDE1和CaN表明，AC和CaN对Ca(2+)的需求受用于刺激它们的信号的不同特性动态调节，因为它们与Ca(2+)的相互作用通常发生在动力学控制下。相反，PDE1对不同Ca(2+)瞬变的即时幅度做出反应，并且通常具有在稳态下观察到的相同Ca(2+)需求。因此，AC、PDE1和CaN解码Ca(2+)信号的不同动态特性。
