DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific.
DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific.
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DOI：
10.1016/j.celrep.2017.05.068
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发表时间：
2017-06-13
期刊：
影响因子：
8.8
通讯作者：
Bayer KU
中科院分区：
文献类型：
--
作者：
Goodell DJ;Zaegel V;Coultrap SJ;Hell JW;Bayer KU
与死亡相关的蛋白激酶1（DAPK1）是神经元细胞死亡的有效介质。在这里，我们发现DAPK1还通过调节Ca2+/钙调蛋白（CAM）依赖性蛋白激酶II（CAMKII）来发挥突触可塑性。长期增强（LTP）和抑郁症（LTD）需要CAMKII和T286-磷酸化，这是两种相反的学习，记忆和认知基础的突触可塑性形式。 T286-磷酸化诱导CAMKII与NMDA受体（NMDAR）亚基Glun2b结合，该亚基glun2b介导了LTP期间CAMKII突触积累。我们发现，CaMKII突触积累的LTP特异性是由于其LTD特异性抑制钙调神经酶（CAN）依赖性DAPK1激活，这又阻止了CAMKII与Glun2b的结合。这种抑制是通过竞争性DAPK1与CAMKII与Glun2b结合来实现的。 Ca2+/CAM对DAPK1/GLUN2B结合的负调控导致LTP期间的突触DAPK1去除，但在LTD期间保留。药物遗传学方法表明，抑制CaMKII/Glun2b结合是LTD所需的DAPK1功能。
Goodell等。发现与长期突触可塑性，有限公司形式需要钙调蛋白（CAN）依赖性蛋白激酶1（DAPK1）的激活。具体而言，DAPK1抑制Ca2+/钙调蛋白依赖性蛋白激酶II（CAMKII）突触积累和LTD期间的Glun2b结合，从而使这些CAMKII机制LTP特异性。
The death associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286-autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP-specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca2+/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD. Goodell et al. find that calcineurin (CaN)-dependent activation of the death associated protein kinase 1 (DAPK1) is required for a form of long-term synaptic plasticity, LTD. Specifically, DAPK1 suppresses Ca2+/calmodulin-dependent protein kinase II (CaMKII) synaptic accumulation and GluN2B binding during LTD, thus making these CaMKII mechanisms LTP-specific.
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影响因子：
5.3
作者：
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