Evidence for cell autonomous AP1 function in regulation of Drosophila motor-neuron plasticity.

Evidence for cell autonomous AP1 function in regulation of Drosophila motor-neuron plasticity.
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DOI:
10.1186/1471-2202-4-20
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发表时间:
2003-09-11
期刊:
影响因子:
2.4
通讯作者:
Ramaswami M
Ramaswami M
中科院分区:
医学4区
文献类型:
--
作者:
Sanyal S;Narayanan R;Consoulas C;Ramaswami M

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转录因子AP1介导脊椎动物和无脊椎动物中枢神经系统的长期可塑性。最近对活动诱导的突触变化的研究表明,AP1可以在CREB上游发挥作用,调节CREB依赖性突触强度增强以及CREB非依赖性果蝇神经肌肉连接处(NMJ)钮扣数的增加。然而,本研究尚不清楚AP1是否在运动神经元中自主地直接调节可塑性。在这里,我们发现AP1的两个组成部分Fos和Jun在运动神经元中大量表达。我们进一步结合免疫组织化学和电生理分析,并使用一系列严格限制AP1转基因在神经系统内表达的增强子,表明AP1在运动神经元内而不是在运动神经元外的诱导或抑制是调节NMJ大小和强度的必要和充分条件。通过反驳AP1对NMJ的影响是通过多突触机制发生的可能性,这些观察结果支持了AP1通过运动神经元的细胞自主通路直接调节NMJ可塑性过程的模型。本文描述的方法可以作为一种有用的实验范式,用于分析影响果蝇运动神经元结构和功能的基因的细胞自主性。
The transcription factor AP1 mediates long-term plasticity in vertebrate and invertebrate central nervous systems. Recent studies of activity-induced synaptic change indicate that AP1 can function upstream of CREB to regulate both CREB-dependent enhancement of synaptic strength as well as CREB-independent increase in bouton number at the Drosophila neuromuscular junction (NMJ). However, it is not clear from this study if AP1 functions autonomously in motor neurons to directly modulate plasticity. Here, we show that Fos and Jun, the two components of AP1, are abundantly expressed in motor neurons. We further combine immunohistochemical and electrophysiological analyses with use of a collection of enhancers that tightly restrict AP1 transgene expression within the nervous system to show that AP1 induction or inhibition in, but not outside of, motor neurons is necessary and sufficient for its modulation of NMJ size and strength. By arguing against the possibility that AP1 effects at the NMJ occur via a polysynaptic mechanism, these observations support a model in which AP1 directly modulates NMJ plasticity processes through a cell autonomous pathway in the motor neuron. The approach described here may serve as a useful experimental paradigm for analyzing cell autonomy of genes found to influence structure and function of Drosophila motor neurons.
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