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首页> 外文期刊>The European Journal of Neuroscience >Multiple determinants in voltage-dependent P/Q calcium channels control their retention in the endoplasmic reticulum.
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Multiple determinants in voltage-dependent P/Q calcium channels control their retention in the endoplasmic reticulum.

机译：电压依赖性P / Q钙通道中的多个决定因素控制它们在内质网中的保留。

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摘要

Surface expression level of voltage-dependent calcium channels is tightly controlled in neurons to avoid the resulting cell toxicity generally associated with excessive calcium entry. Cell surface expression of high voltage-activated calcium channels requires the association of the pore-forming subunit, Cavalpha, with the auxiliary subunit, Cavbeta. In the absence of this auxiliary subunit, Cavalpha is retained in the endoplasmic reticulum (ER) through mechanisms that are still poorly understood. Here, we have investigated, by a quantitative method based on the use of CD8 alpha chimeras, the molecular determinants of Cavalpha2.1 that are responsible for the retention, in the absence of auxiliary subunits, of P/Q calcium channels in the ER (referred to here as 'ER retention'). This study demonstrates that the I-II loop of Cavalpha2.1 contains multiple ER-retention determinants beside the beta subunit association domain. In addition, the I-II loop is not the sole domain of calcium channel retention as two regions identified for their ability to interact with the I-II loop, the N- and C-termini of Cavalpha2.1, also produce ER retention. It is also not an obligatory determinant as, similarly to low-threshold calcium channels, the I-II loop of Cavalpha1.1 does not produce ER retention in COS7 cells. The data presented here suggests that ER retention is suppressed by sequential molecular events that include: (i). a correct folding of Cavalpha in order to mask several internal ER-retention determinants and (ii). the association of other proteins, including the Cavbeta subunit, to suppress the remaining ER-retention determinants.
机译：电压依赖性钙通道的表面表达水平在神经元中受到严格控制，以避免通常与过量钙进入相关的最终细胞毒性。高压激活钙通道的细胞表面表达需要孔形成亚基Cavalpha与辅助亚基Cavbeta的关联。在缺少这种辅助亚基的情况下，Cavalpha通过尚不清楚的机制保留在内质网（ER）中。在这里，我们已经通过基于CD8α嵌合体的定量方法研究了Cavalpha2.1的分子决定簇，这些分子决定簇在没有辅助亚基的情况下在ER中保留了P / Q钙通道（在这里称为“ ER保留”）。这项研究表明，Cavalpha2.1的I-II环除β亚基缔合域外还包含多个ER保留决定簇。此外，I-II环不是钙通道保留的唯一区域，因为两个区域因其与I-II环的相互作用而被识别，Cavalpha2.1的N-和C-末端也可产生ER保留。它也不是强制性的决定因素，因为类似于低阈值钙通道，Cavalpha1.1的I-II环不会在COS7细胞中产生ER滞留。此处提供的数据表明，ER保留被连续的分子事件抑制，这些事件包括：（i）。正确折叠Cavalpha，以掩盖多个内部ER保留决定簇和（ii）。包括Cavbeta亚基在内的其他蛋白质的缔合，以抑制剩余的ER保留决定簇。

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