Calmodulin dependent protein kinase increases conductance at gap junctions formed by the neuronal gap junction protein connexin36.
Calmodulin dependent protein kinase increases conductance at gap junctions formed by the neuronal gap junction protein connexin36.
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钙调蛋白依赖性蛋白激酶在由神经元间隙连接蛋白连接蛋白结构36形成的间隙连接处增加了电导。
DOI：
10.1016/j.brainres.2012.06.058
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发表时间：
2012-12-03
期刊：
影响因子：
2.9
通讯作者：
Spray DC
中科院分区：
文献类型：
--
作者：
Del Corsso C;Iglesias R;Zoidl G;Dermietzel R;Spray DC
主要神经元间隙连接蛋白 Connexin 36 (Cx36) 表现出显着的“助跑”特性，其中连接电导通常在使用贴片移液器磨合细胞后 5-10 分钟内增加十倍或更多。这种电导“上升”是 Cx36 的独特特性，因为在表达其他连接蛋白的细胞对中尚未发现。由于最近描述了 Cx36 中 CaMKII 结合和磷酸化位点的观察结果以及钙调蛋白依赖性蛋白激酶 II (CaMKII) 可能增强硬骨鱼神经元中的电耦合的证据，我们探索了 CaMKII 是否激活哺乳动物 Cx36。与该假设一致，缺乏CaMKII结合和磷酸化位点的某些Cx36突变体或用对应于结合或磷酸化位点的某些同源肽处理的野生型Cx36阻断或强烈减弱了连接电导的上升。同样，CaMKII 的抑制剂 KN-93 会阻止启动，与 CaMKII 自抑制结构域相对应的膜渗透肽也是如此。此外，启动被移液管内递送的磷酸酶阻断，并且不受磷酸酶抑制剂冈田酸处理的影响。这些结果意味着 CaMKII 的磷酸化增强了 Cx36 通道的连接电流，从而赋予由该蛋白形成的电突触功能可塑性。
The major neuronal gap junction protein Connexin 36 (Cx36) exhibits the remarkable property of “run-up”, in which junctional conductance typically increases by ten-fold or more within 5–10 min following cell break-in with patch pipettes. Such conductance “run-up” is a unique property of Cx36, as it has not been seen in cell pairs expressing other connexins. Because of the recent observation describing CaMKII binding and phosphorylation sites in Cx36 and evidence that calmodulin dependent protein kinase II (CaMKII) may potentiate electrical coupling in neurons of teleosts, we have explored whether CaMKII activates mammalian Cx36. Consistent with this hypothesis, certain Cx36 mutants lacking the CaMKII binding and phosphorylation sites or wild type Cx36 treated with certain cognate peptides corresponding to binding or phosphorylation sites blocked or strongly attenuated run-up of junctional conductance. Likewise, KN-93, an inhibitor of CaMKII, blocked run-up, as did a membrane permeable peptide corresponding to the CaMKII autoinhibitory domain. Furthermore, run-up was blocked by phosphatase delivered within the pipette and not affected by treatment with the phosphatase inhibitor okadaic acid. These results imply that phosphorylation by CaMKII strengthens junctional currents of Cx36 channels, thereby conferring functional plasticity on electrical synapses formed of this protein.
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DOI：
10.1073/pnas.0805408105
发表时间：
2008-12-30
影响因子：
11.1
作者：
Alev, Cantas;Urschel, Stephanie;Dermietzel, Rolf
通讯作者：
Dermietzel, Rolf
DOI：
10.1073/pnas.0734299100
发表时间：
2003-04-15
影响因子：
11.1
作者：
Smith, M;Pereda, AE
通讯作者：
Pereda, AE
影响因子：
3.4
作者：
Hombach, S;Janssen-Bienhold, U;Willecke, K
通讯作者：
Willecke, K
影响因子：
16.2
作者：
Cachope, Roger;Mackie, Ken;Pereda, Alberto E.
通讯作者：
Pereda, Alberto E.
影响因子：
3.5
作者：
Kreuzberg, Maria M.;Deuchars, Jim;Willecke, Klaus
通讯作者：
Willecke, Klaus