The neuronal connexin36 interacts with and is phosphorylated by CaMKII in a way similar to CaMKII interaction with glutamate receptors
The neuronal connexin36 interacts with and is phosphorylated by CaMKII in a way similar to CaMKII interaction with glutamate receptors
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DOI：
10.1073/pnas.0805408105
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发表时间：
2008-12-30
影响因子：
11.1
通讯作者：
Dermietzel, Rolf
中科院分区：
文献类型：
--
作者：
Alev, Cantas;Urschel, Stephanie;Dermietzel, Rolf
电突触可以经历活动依赖的可塑性。钙/钙调蛋白依赖性激酶II（CaMKII）似乎在这种现象中发挥关键作用，但CaMKII如何影响神经元间隙连接蛋白连接蛋白36（Cx 36）的潜在机制尚不清楚。在这里，我们证明了有效的结合S-35-标记的CaMKII的Cx 36和在体外磷酸化这种蛋白质的激酶的胞膜胞质结构域。这两个域揭示了惊人的相似性与部分的调节亚基的CaMKII，其中包括pseudosubstrate和pseudotarget网站的激酶。与NMDA受体的NR 2B亚基类似，Cx 36结合位点均表现出磷酸化依赖性相互作用和CaMKII的自主激活。CaMKII和Cx 36被证明是显着共定位在下橄榄，脑干核高度富集电突触，表明这些蛋白质的物理接近。在类比NR 2B与CaMKII相互作用的当前概念，我们提出了一个模型，提供了一个机械框架CaMKII和Cx 36在电突触的相互作用。
Electrical synapses can undergo activity-dependent plasticity. The calcium/calmodulin-dependent kinase II (CaMKII) appears to play a critical role in this phenomenon, but the underlying mechanisms of how CaMKII affects the neuronal gap junction protein connexin36 (Cx36) are unknown. Here we demonstrate effective binding of S-35-labeled CaMKII to 2 juxtamembrane cytoplasmic domains of Cx36 and in vitro phosphorylation of this protein by the kinase. Both domains reveal striking similarities with segments of the regulatory subunit of CaMKII, which include the pseudosubstrate and pseudotarget sites of the kinase. Similar to the NR2B subunit of the NMDA receptor both Cx36 binding sites exhibit phosphorylation-dependent interaction and autonomous activation of CaMKII. CaMKII and Cx36 were shown to be significantly colocalized in the inferior olive, a brainstem nucleus highly enriched in electrical synapses, indicating physical proximity of these proteins. In analogy to the current notion of NR2B interaction with CaMKII, we propose a model that provides a mechanistic framework for CaMKII and Cx36 interaction at electrical synapses.