CaMKII phosphorylates a threonine residue in the C-terminal tail of Cav1.2 Ca2+ channel and modulates the interaction of the channel with calmodulin
CaMKII phosphorylates a threonine residue in the C-terminal tail of Cav1.2 Ca2+ channel and modulates the interaction of the channel with calmodulin
复制标题
CaMKII 磷酸化 Cav1.2 Ca2 通道 C 末端尾部的苏氨酸残基，并调节通道与钙调蛋白的相互作用
DOI：
10.1007/s12576-009-0033-y
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发表时间：
2009-07-01
影响因子：
2.3
通讯作者：
Kameyama, Masaki
中科院分区：
文献类型：
--
作者：
Wang, Wu-Yang;Hao, Li-Ying;Kameyama, Masaki
我们以前已经发现，CaMKII介导的磷酸化和钙调素（CaM）结合到通道是维持Cav1.2钙通道的基础活性所必需的。在这项研究中，我们研究了假设CaMKII磷酸化位点Cav1.2，有助于通道调节。我们发现，CaMK II磷酸化Thr 1603残基（Thr 1604在兔）内的preIQ区域在豚鼠Cav1.2通道的C-末端尾部。Thr 1603突变为Asp（T1603 D）减缓了内面向外补丁模式下通道的下降，并消除了CaM逆转下降效应的时间依赖性。我们还发现，CaMKII介导的近端C-末端片段（CT 1）的磷酸化增加，而CT 1的去磷酸化降低了其与CaM的结合。这些发现表明，CaMK Ⅱ调节CaM结合到通道，从而维持Cav1.2 Ca 2+通道的基础活性。
We have previously found that both CaMKII-mediated phosphorylation and calmodulin (CaM) binding to the channels are required for maintaining basal activity of the Cav1.2 Ca2+ channels. In this study, we investigated the hypothetical CaMKII phosphorylation site on Cav1.2 that contributes to the channel regulation. We found that CaMKII phosphorylates the Thr1603 residue (Thr1604 in rabbit) within the preIQ region in the C-terminal tail of the guinea-pig Cav1.2 channel. Mutation of Thr1603 to Asp (T1603D) slowed the run-down of the channel in inside-out patch mode and abolished the time-dependency of the CaM’s effects to reverse run-down. We also found that CaMKII-mediated phosphorylation of the proximal C-terminal fragment (CT1) increased, while dephosphorylation of CT1 decreased its binding with CaM. These findings suggest that CaMKII regulates the CaM binding to the channel, and thereby maintains basal activity of the Cav1.2 Ca2+ channel.