Phosphorylation of Complexin by PKA Regulates Activity-Dependent Spontaneous Neurotransmitter Release and Structural Synaptic Plasticity.
Phosphorylation of Complexin by PKA Regulates Activity-Dependent Spontaneous Neurotransmitter Release and Structural Synaptic Plasticity.
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DOI：
10.1016/j.neuron.2015.10.011
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发表时间：
2015-11-18
期刊：
影响因子：
16.2
通讯作者：
Littleton JT
中科院分区：
文献类型：
--
作者：
Cho RW;Buhl LK;Volfson D;Tran A;Li F;Akbergenova Y;Littleton JT
突触可塑性是神经系统的一个基本特征，它允许适应不断变化的行为环境。大多数关于突触可塑性的研究都研究了突触后谷氨酸受体的调节性运输，这些受体在突触传递中产生改变。突触前释放机制的变化是否以及如何影响神经元的可塑性尚不清楚。SNARE复合物介导神经递质释放以响应突触前Ca++进入。在这里，我们表明，SNARE融合钳复合蛋白经历活性依赖性磷酸化，改变了果蝇神经传递的基本特性。刺激后的逆行信号传导激活复合蛋白C末端的PKA依赖性磷酸化，其选择性地和瞬时地增强自发释放。活性依赖性突触生长需要增强的自发释放。这些数据表明，SNARE依赖的融合机制可以以活性依赖的方式进行调节，并突出了自发神经递质释放作为功能和结构可塑性介质的关键作用。
Synaptic plasticity is a fundamental feature of the nervous system that allows adaptation to changing behavioral environments. Most studies of synaptic plasticity have examined the regulated trafficking of postsynaptic glutamate receptors that generates alterations in synaptic transmission. Whether and how changes in the presynaptic release machinery contribute to neuronal plasticity is less clear. The SNARE complex mediates neurotransmitter release in response to presynaptic Ca++ entry. Here we show that the SNARE fusion clamp Complexin undergoes activity-dependent phosphorylation that alters the basic properties of neurotransmission in Drosophila. Retrograde signaling following stimulation activates PKA-dependent phosphorylation of the Complexin C-terminus that selectively and transiently enhances spontaneous release. Enhanced spontaneous release is required for activity-dependent synaptic growth. These data indicate that SNARE-dependent fusion mechanisms can be regulated in an activity-dependent manner and highlight the key role of spontaneous neurotransmitter release as a mediator of functional and structural plasticity.