Subsynaptic AMPA receptor distribution is acutely regulated by actin-driven reorganization of the postsynaptic density.
Subsynaptic AMPA receptor distribution is acutely regulated by actin-driven reorganization of the postsynaptic density.
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DOI：
10.1523/jneurosci.2927-11.2012
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发表时间：
2012-01-11
期刊：
影响因子：
--
通讯作者：
Blanpied TA
中科院分区：
文献类型：
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作者：
Kerr JM;Blanpied TA
AMPA受体（AMPAR）在学习、发育和疾病过程中介导突触传递和可塑性。决定突触下受体位置的机制知之甚少，但却是量子大小的关键决定因素。我们使用了一系列的活细胞，高分辨率成像方法来测量蛋白质组织内单个突触后密度在大鼠海马神经元。通过突触亚结构域中的光漂白受体，我们发现大多数AMPAR不能在突触内自由扩散，这表明它们嵌入在决定其突触下位置的基质中。然而，时间推移分析表明，突触AMPAR不断重新定位与可塑性的这种支架基质，而不是简单地通过自由扩散。使用荧光相关性分析，我们发现，在横向范围内的单一PSD，组件蛋白质的差异分布，并不断调整肌动蛋白酶的铣削这种分布。GluA 1的C-末端PDZ配体不调节其在突触中的移动性或分布。然而，谷氨酸受体激活促进突触下的流动性。引人注目的是，即使在肌动蛋白丝丢失后，AMPAR和支架分子的突触下不动性基本上保持完整。我们的结论是，受体积极重新定位在突触的肌动蛋白细胞骨架，影响，这是间接传递给受体通过柔韧的和令人惊讶的动态内部结构的PSD。
AMPA receptors (AMPARs) mediate synaptic transmission and plasticity during learning, development, and disease. Mechanisms determining subsynaptic receptor position are poorly understood but are key determinants of quantal size. We used a series of live-cell, high-resolution imaging approaches to measure protein organization within single postsynaptic densities in rat hippocampal neurons. By photobleaching receptors in synapse subdomains, we found that most AMPARs do not freely diffuse within the synapse, indicating they are embedded in a matrix that determines their subsynaptic position. However, time lapse analysis revealed that synaptic AMPARs are continuously repositioned in concert with plasticity of this scaffold matrix rather than simply by free diffusion. Using a fluorescence correlation analysis, we found that across the lateral extent of single PSDs, component proteins were differentially distributed, and this distribution was continually adjusted by actin treadmilling. The C-terminal PDZ ligand of GluA1 did not regulate its mobility or distribution in the synapse. However, glutamate receptor activation promoted subsynaptic mobility. Strikingly, subsynaptic immobility of both AMPARs and scaffold molecules remained essentially intact even after loss of actin filaments. We conclude that receptors are actively repositioned at the synapse by treadmilling of the actin cytoskeleton, an influence which is transmitted only indirectly to receptors via the pliable and surprisingly dynamic internal structure of the PSD.