Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: A study with knockout mice
Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: A study with knockout mice
复制标题
DOI：
10.1073/pnas.210184697
复制
发表时间：
2000-10-10
影响因子：
11.1
通讯作者：
Huang, KP
中科院分区：
文献类型：
--
作者：
Pak, JH;Huang, FL;Huang, KP
Neurogranin/RC3 是一种神经特异性 Ca2+ 敏感钙调蛋白 (CaM) 结合蛋白，其 Cam 结合亲和力通过磷酸化和氧化调节。我们在此表明，小鼠中 Ng 基因的缺失不会导致明显的发育或神经解剖学异常，但会导致空间学习受损以及海马短期和长期可塑性变化（配对脉冲抑制、突触疲劳、长期增强诱导）。这些缺陷伴随着激活的 Ca2+/CaM 依赖性激酶 II (CaMKII) 基础水平的降低（约为野生型的 60%）。此外，分别用冈田酸和硝普钠刺激蛋白质磷酸化和氧化后，突变小鼠的海马切片显示出生成活化 CaMKII 的能力降低。这些结果表明 Ng 在 CaMKII 活性调节中发挥核心作用，对突触可塑性和空间学习具有决定性影响。
Neurogranin/RC3 is a neural-specific Ca2+-sensitive calmodulin (CaM)-binding protein whose Cam-binding affinity is modulated by phosphorylation and oxidation, Here we show that deletion of the Ng gene in mice did not result in obvious developmental or neuroanatomical abnormalities but caused an impairment of spatial learning and changes in hippocampal short- and long-term plasticity (paired-pulse depression, synaptic fatigue, long-term potentiation induction). These deficits were accompanied by a decreased basal level of the activated Ca2+/CaM-dependent kinase II (CaMKII) (approximate to 60% of wild type). Furthermore, hippocampal slices of the mutant mice displayed a reduced ability to generate activated CaMKII after stimulation of protein phosphorylation and oxidation by treatments with okadaic acid and sodium nitroprusside, respectively. These results indicate a central role of Ng in the regulation of CaMKII activity with decisive influences on synaptic plasticity and spatial learning.