A hierarchy of cell intrinsic and target-derived homeostatic signaling.

A hierarchy of cell intrinsic and target-derived homeostatic signaling.
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DOI:
10.1016/j.neuron.2010.03.023
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发表时间:
2010-04-29
期刊:
影响因子:
16.2
通讯作者:
Davis, Graeme W.
Davis, Graeme W.
中科院分区:
医学1区
文献类型:
--
作者:
Bergquist, Sharon;Dickman, Dion K.;Davis, Graeme W.

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神经功能的动态平衡控制可以通过调节离子通道的表达、神经递质受体的丰度或调节突触前释放来实现。这些过程可以通过细胞自主或细胞间信号来实现。目前尚不清楚不同形式的动态平衡调节是否能够协调一致,以实现恒定的神经功能。解决这个问题的一种方法是面对一个简单的神经系统,面对相互冲突的扰动,并确定结果是否反映了协调的、内环境平衡的反应。在这里,我们证明了两个A-型钾通道基因,shal和shaker,是相互的,转录偶联,以维持A-型通道的表达。然后,我们证明了A型通道表达的这种动态平衡控制阻止了突触传递的靶点依赖的动态平衡调节。因此,我们发现了一种相互调节A型钾通道的新的动态平衡机制,并定义了细胞内在控制离子通道表达和靶向派生的动态平衡控制突触传递之间的等级关系。
Homeostatic control of neural function can be mediated by the regulation of ion channel expression, neurotransmitter receptor abundance, or modulation of presynaptic release. These processes can be implemented through cell autonomous or intercellular signaling. It remains unknown whether different forms of homeostatic regulation can be coordinated to achieve constant neural function. One way to approach this question is to confront a simple neural system with conflicting perturbations and determine whether the outcome reflects a coordinated, homeostatic response. Here we demonstrate that two A-type potassium channel genes, shal and shaker, are reciprocally, transcriptionally coupled to maintain A-type channel expression. We then demonstrate that this homeostatic control of A-type channel expression prevents target-dependent, homeostatic modulation of synaptic transmission. Thus, we uncover a novel homeostatic mechanism that reciprocally regulates A-type potassium channels and we define a hierarchical relationship between cell-intrinsic control of ion channel expression and target-derived homeostatic control of synaptic transmission.
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