Apparent lack of physical or functional interaction between CaV1.1 and its distal C terminus.
Apparent lack of physical or functional interaction between CaV1.1 and its distal C terminus.
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DOI：
10.1085/jgp.201411292
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Beam KG
中科院分区：
文献类型：
--
作者：
Ohrtman JD;Romberg CF;Moua O;Bannister RA;Levinson SR;Beam KG
CaV1.1的远端C-末端结构域对于骨骼肌中L-型Ca 2+电流的去极化诱导增强不是必需的。CaV1.1既是触发骨骼肌兴奋-收缩偶联的电压传感器，又是L型Ca 2+通道。有人提出，在其翻译后裂解，CaV1.1的远端C末端仍然与近端CaV1.1非共价结合，并且蛋白激酶A与远端C末端的拴系是骨骼肌中L-型Ca 2+电流去极化诱导增强所需的。在这里，我们报告说，协会的远端C末端与近端CaV1.1不能检测到的小鼠骨骼肌的免疫沉淀或共定位荧光后，在成人骨骼肌纤维的CaV1.1结构标记的黄色荧光蛋白（YFP）和青色荧光蛋白的N和C末端，分别。我们发现，L型钙通道活性是相似的表达后的结构，无论是做（YFP-CaV 1.11860）或不（YFP-CaV 1.11666）含有编码序列的远端C-末端结构域在非基因型肌管无效的内源性CaV 1. 1。此外，在响应强（高达90 mV）或持久的前脉冲（高达200 ms），尾电流幅度和衰减时间同样增加在发育不良的肌管表达YFP-CaV 1.11860或YFP-CaV 1.11666，这表明远端C-末端结构域是不需要去极化诱导的增强。因此，我们的实验不支持近端CaV1.1和远端C末端之间存在生物化学或功能相互作用。
The distal C-terminal domain of CaV1.1 is not required for depolarization-induced potentiation of L-type Ca2+ current in skeletal muscle. CaV1.1 acts as both the voltage sensor that triggers excitation–contraction coupling in skeletal muscle and as an L-type Ca2+ channel. It has been proposed that, after its posttranslational cleavage, the distal C terminus of CaV1.1 remains noncovalently associated with proximal CaV1.1, and that tethering of protein kinase A to the distal C terminus is required for depolarization-induced potentiation of L-type Ca2+ current in skeletal muscle. Here, we report that association of the distal C terminus with proximal CaV1.1 cannot be detected by either immunoprecipitation of mouse skeletal muscle or by colocalized fluorescence after expression in adult skeletal muscle fibers of a CaV1.1 construct labeled with yellow fluorescent protein (YFP) and cyan fluorescent protein on the N and C termini, respectively. We found that L-type Ca2+ channel activity was similar after expression of constructs that either did (YFP-CaV1.11860) or did not (YFP-CaV1.11666) contain coding sequence for the distal C-terminal domain in dysgenic myotubes null for endogenous CaV1.1. Furthermore, in response to strong (up to 90 mV) or long-lasting prepulses (up to 200 ms), tail current amplitudes and decay times were equally increased in dysgenic myotubes expressing either YFP-CaV1.11860 or YFP-CaV1.11666, suggesting that the distal C-terminal domain was not required for depolarization-induced potentiation. Thus, our experiments do not support the existence of either biochemical or functional interactions between proximal CaV1.1 and the distal C terminus.
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影响因子：
5.5
作者：
Held, B;Freise, D;Flockerzi, V
通讯作者：
Flockerzi, V
DOI：
10.1073/pnas.88.23.10778
发表时间：
1991-12-01
影响因子：
11.1
作者：
DEJONGH, KS;WARNER, C;CATTERALL, WA
通讯作者：
CATTERALL, WA
影响因子：
4.8
作者：
Grabner, M;Dirksen, RT;Beam, KG
通讯作者：
Beam, KG
影响因子：
64.8
作者：
BEAM, KG;ADAMS, BA;TANABE, T
通讯作者：
TANABE, T
影响因子：
3.8
作者：
BEAM, KG;KNUDSON, CM
通讯作者：
KNUDSON, CM