NMDA 诱导 Shank 在突触后密度处的积累是由 CaMKII 介导的。
NMDA-induced accumulation of Shank at the postsynaptic density is mediated by CaMKII.
机构信息
EM Facility, NINDS, NIH, Bethesda, MD, United States.
Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD, United States.
出版信息
Biochem Biophys Res Commun. 2014 Jul 18;450(1):808-11. doi: 10.1016/j.bbrc.2014.06.049. Epub 2014 Jun 19.
Shank is a specialized scaffold protein present in high abundance at the postsynaptic density (PSD). Using pre-embedding immunogold electron microscopy on cultured hippocampal neurons, we had previously demonstrated further accumulation of Shank at the PSD under excitatory conditions. Here, using the same experimental protocol, we demonstrate that a cell permeable CaMKII inhibitor, tatCN21, blocks NMDA-induced accumulation of Shank at the PSD. Furthermore we show that NMDA application changes the distribution pattern of Shank at the PSD, promoting a 7-10 nm shift in the median distance of Shank labels away from the postsynaptic membrane. Inhibition of CaMKII with tatCN21 also blocks this shift in the distribution of Shank. Altogether these results imply that upon activation of NMDA receptors, CaMKII mediates accumulation of Shank, preferentially at the distal regions of the PSD complex extending toward the cytoplasm.
Shank 是一种丰富表达于突触后密度（PSD）的支架蛋白。我们之前通过培养的海马神经元的包埋前免疫金电子显微镜技术证明，在兴奋性条件下 PSD 处的 Shank 进一步聚集。在这里，我们使用相同的实验方案证明细胞可渗透的 CaMKII 抑制剂 tatCN21 阻断 NMDA 诱导的 PSD 处 Shank 的积累。此外，我们还表明，NMDA 的应用改变了 PSD 处 Shank 的分布模式，促进了 Shank 标记物从突触后膜的中位数距离向 7-10nm 的转移。用 tatCN21 抑制 CaMKII 也阻止了 Shank 分布的这种转移。总的来说，这些结果表明，在 NMDA 受体激活后，CaMKII 介导 Shank 的积累，优先在伸向细胞质的 PSD 复合物的远端区域。
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