α- and βCaMKII:: Inverse regulation by neuronal activity and opposing effects on synaptic strength
α- and βCaMKII:: Inverse regulation by neuronal activity and opposing effects on synaptic strength
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DOI：
10.1016/s0896-6273(02)01049-8
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发表时间：
2002-12-19
期刊：
影响因子：
16.2
通讯作者：
Tsien, RW
中科院分区：
文献类型：
--
作者：
Thiagarajan, TC;Piedras-Renteria, ES;Tsien, RW
我们发现，在培养的海马神经元中，α和β CaMKII受活动的负调控：α/β比值在活动增加期间向α移动，在活动减少期间向β移动。比值的变化接近5倍，这可能有助于调节CaMKII全酶以改变Ca 2+信号的强度。CaMKII水平的调节使用可区分的途径，一种对单独控制alphaCaMKII的NMDA受体阻断起反应，另一种对AMPA受体阻断起反应并涉及betaCaMKII以及betaCaMKII对alphaCaMKII的可能的进一步下游作用。α CaMKII或β CaMKII的过表达导致对单一突触强度以及mEPSC频率的相反作用，这可以部分解释AMPA受体慢性阻断所观察到的活性依赖性作用。调节CaMKII亚基的组成可能是重要的活动依赖性突触稳态和可塑性。
We show that a and betaCaMKII are inversely regulated by activity in hippocampal neurons in culture: the alpha/beta ratio shifts toward alpha during increased activity and beta during decreased activity. The swing in ratio is similar to5-fold and may help tune the CaMKII holoenzyme to changing intensities of Ca2+ signaling. The regulation of CaMKII levels uses distinguishable pathways, one responsive to NMDA receptor blockade that controls alphaCaMKII alone, the other responsive to AMPA receptor blockade and involving betaCaMKII and possibly further downstream effects of betaCaMKII on alphaCaMKII. Overexpression of alphaCaMKII or betaCaMKII resulted in opposing effects on unitary synaptic strength as well as mEPSC frequency that could account in part for activity-dependent effects observed with chronic blockade of AMPA receptors. Regulation of CaMKII subunit composition may be important for both activity-dependent synaptic homeostasis and plasticity.