Autonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation.
Autonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation.
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DOI：
10.1523/jneurosci.0133-10.2010
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发表时间：
2010-06-30
期刊：
影响因子：
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通讯作者：
Lisman J
中科院分区：
文献类型：
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作者：
Pi HJ;Otmakhov N;Lemelin D;De Koninck P;Lisman J
CaMKII是长时程增强（LTP）的关键中介。急性细胞内注射具有催化活性的CaMKII片段使LTP饱和，而在转基因小鼠中表达的CaMKII全酶的自主活性形式（T286D）没有饱和增强。为了更好地理解全酶在控制突触强度中的作用，我们用编码CaMKII的结构体转染海马神经元，模拟不同的磷酸化状态。令人惊讶的是，T286D不仅不能增强突触强度，而且通过ltd样过程产生突触抑制。T305/T306磷酸化对这种抑制至关重要，因为假磷酸化形式（T286D/T305D/T306D）的过度表达导致抑制LTD，而T305/T306不能磷酸化的自主形式（T286D/T305A/T306A）的过度表达阻止LTD（相反产生增强）。因此，自主CaMKII可以导致LTP或LTD，这取决于控制点T305/T306的磷酸化状态。
CaMKII is a key mediator of long-term potentiation (LTP). Whereas acute intracellular injection of catalytically active CaMKII fragments saturates LTP, an autonomously active form (T286D) of CaMKII holoenzyme expressed in transgenic mice did not saturate potentiation. To better understand the role of the holoenzyme in the control of synaptic strength, we transfected hippocampal neurons with constructs encoding forms of CaMKII mimicking different phosphorylation states. Surprisingly, T286D not only failed to potentiate synaptic strength, but produced synaptic depression through an LTD-like process. T305/T306 phosphorylation was critical for this depression because overexpression of the pseudophosphorylated form (T286D/T305D/T306D) caused depression that occluded LTD, and overexpression of an autonomous form in which T305/T306 could not be phosphorylated (T286D/T305A/T306A) prevented LTD (instead producing potentiation). Therefore, autonomous CaMKII can lead to either LTP or LTD, depending on the phosphorylation state of the control point, T305/T306.