Quantitative estimates of the cytoplasmic, PSD, and NMDAR-bound pools of CaMKII in dendritic spines.
Quantitative estimates of the cytoplasmic, PSD, and NMDAR-bound pools of CaMKII in dendritic spines.
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DOI：
10.1016/j.brainres.2011.08.051
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发表时间：
2011-10-24
期刊：
影响因子：
2.9
通讯作者：
Lisman J
中科院分区：
文献类型：
--
作者：
Feng B;Raghavachari S;Lisman J
CaMKII在长时程增强（LTP）中起关键作用。该激酶是突触后密度（PSD）的主要成分;然而，它也包含在棘细胞质中。CaMKII现在可以在活的神经元中进行光学监测，因此重要的是要了解PSD和细胞质池对光信号的贡献。在这里，我们估计的基础条件下，这些池的大小。根据EM免疫标记数据，我们计算出PSD/细胞质比率约为5%。第二个独立的估计是来自测量表明，平均蘑菇刺PSD包含90至240全酶。根据海马组织的总CaMKII含量、不同隔室的相对体积和CaMKII的棘-树突比（2：1），可以估计棘中16 µM（约2590种全酶）的细胞质浓度。这些数字产生PSD/脊柱比的第二个估计值（6%），与第一个估计值非常一致。与NMDAR结合的CaMKII是重要的，因为阻止这种复合物的形成会阻断LTP诱导。我们估计通过结合NMDAR而保持活性的棘CaMKII的百分比为~ 0.2%。高脊柱浓度的CaMKII（> 100微摩尔α亚基）和PSD内的小部分的影响进行了讨论。特别值得注意的是，在LTP诱导后，棘中的CaMKII信号仅显示短暂激活（开放状态）的发现受到以下限制：它不反映与NMDAR结合的小但重要的库。
CaMKII plays a critical role in long-term potentiation (LTP). The kinase is a major component of the postsynaptic density (PSD); however, it is also contained in the spine cytoplasm. CaMKII can now be monitored optically in living neurons, and it is therefore important to understand the contribution of the PSD and cytoplasmic pools to optical signals. Here, we estimate the size of these pools under basal conditions. From EM immunolabeling data, we calculate that the PSD/cytoplasmic ratio is ~5%. A second independent estimate is derived from measurements indicating that the average mushroom spine PSD contains 90 to 240 holoenzymes. A cytoplasmic concentration of 16 µM (~2590 holoenzymes) in the spine can be estimated from the total measured CaMKII content of hippocampal tissue, the relative volume of different compartments, and the spine-dendrite ratio of CaMKII (2:1). These numbers yield a second estimate (6%) of the PSD/spine ratio in good agreement with the first. The CaMKII bound to the NMDAR is important because preventing the formation of this complex blocks LTP induction. We estimate that the percentage of spine CaMKII held active by binding to the NMDAR is ~0.2%. Implications of the high spine concentration of CaMKII (> 100 micromolar alpha subunits) and the small fraction within the PSD are discussed. Of particular note, the finding that the CaMKII signal in spines shows only transient activation (open state) after LTP induction is subject to the qualification that it does not reflect the small but important pool bound to the NMDAR.
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