Homeostatic regulation of AMPA receptor trafficking and degradation by light-controlled single-synaptic activation.
Homeostatic regulation of AMPA receptor trafficking and degradation by light-controlled single-synaptic activation.
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通过光控制的单突触激活对AMPA受体运输和降解的稳态调节。
DOI：
10.1016/j.neuron.2011.10.011
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发表时间：
2011-12-08
期刊：
影响因子：
16.2
通讯作者：
Man HY
中科院分区：
文献类型：
--
作者：
Hou Q;Gilbert J;Man HY
在响应于神经元活动的改变的稳态调节期间，AMPA受体（AMPAR）的突触表达被整体上调或下调，使得神经元活动恢复到生理范围。鉴于中枢神经元接受多个突触前输入，AMPAR突触表达是否以及如何在单个突触中进行稳态调节仍不清楚。在培养的海马神经元中，我们报告说，当一个单独的突触前末梢的活动被选择性地升高，由光控制的兴奋，AMPAR丰度在兴奋的突触选择性下调，在一个NMDAR依赖的方式。表面AMPAR的减少伴随着增强的受体内吞作用并依赖于蛋白酶体活性。突触激活还导致泛素连接酶Nedd4和多聚泛素化水平的位点特异性增加，与脊柱中的AMPAR泛素化和降解一致。这些结果表明，AMPAR积累在个别突触是受自主稳态调节响应突触活动。
During homeostatic adjustment in response to alterations in neuronal activity, synaptic expression of AMPA receptors (AMPARs) is globally tuned up- or down so that the neuronal activity is restored to a physiological range. Given that a central neuron receives multiple presynaptic inputs, whether and how AMPAR synaptic expression is homeostatically regulated at individual synapses remains unclear. In cultured hippocampal neurons, we report that when activity of an individual presynaptic terminal is selectively elevated by light-controlled excitation, AMPAR abundance at the excited synapses is selectively down-regulated in an NMDAR-dependent manner. The reduction in surface AMPARs is accompanied by enhanced receptor endocytosis and dependent on proteasomal activity. Synaptic activation also leads to a site-specific increase in the ubiquitin ligase Nedd4 and polyubiquitination levels, consistent with AMPAR ubiquitination and degradation in the spine. These results indicate that AMPAR accumulation at individual synapses is subject to autonomous homeostatic regulation in response to synaptic activity.
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