Differential association between HERG and KCNE1 or KCNE2.
Differential association between HERG and KCNE1 or KCNE2.
复制标题
HERG和KCNE1或KCNE2之间的差异关联。
DOI：
10.1371/journal.pone.0000933
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发表时间：
2007-09-26
期刊：
影响因子：
3.7
通讯作者：
McDonald, Thomas V.
中科院分区：
文献类型：
--
作者：
Um, Sung Yon;McDonald, Thomas V.
由KCNE 1和KCNE 2编码的小蛋白都被认为是HERG通道的辅助亚基，本文报道了我们对KCNE-HERG相互作用的细胞生物学研究。在共表达系统中，KCNE 1比KCNE 2更容易与共表达的HERG共沉淀。（通过Brefeldin A或在KCNE cDNA上工程化ER保留/恢复信号）KCNE 2的细胞内丰度及其与HERG的结合相对于KCNE 1显著增加。处理细胞的隔室（ER、高尔基体和质膜）。通过表面标记和共聚焦免疫荧光，KCNE 2在细胞表面比KCNE 1更丰富，KCNE 1与ER标记物钙连接蛋白表现出更大的共定位。细胞外培养基的检查表明，大量的KCNE 2是细胞外的（可溶性和膜囊泡相关）。两者合计，这些结果表明，在通道的生物发生过程中，HERG更有可能与KCNE 1比KCNE 2组装，这是由于明显不同的运输速率和在细胞中的保留，而不是相对亲和力的差异。在体内，最终的通道亚基构成可能由相对细胞间表达速率和差异蛋白质加工和运输的组合决定。
The small proteins encoded by KCNE1 and KCNE2 have both been proposed as accessory subunits for the HERG channel. Here we report our investigation into the cell biology of the KCNE-HERG interaction. In a co-expression system, KCNE1 was more readily co-precipitated with co-expressed HERG than was KCNE2. When forward protein trafficking was prevented (either by Brefeldin A or engineering an ER-retention/retrieval signal onto KCNE cDNA) the intracellular abundance of KCNE2 and its association with HERG markedly increased relative to KCNE1. HERG co-localized more completely with KCNE1 than with KCNE2 in all the membrane-processing compartments of the cell (ER, Golgi and plasma membrane). By surface labeling and confocal immunofluorescence, KCNE2 appeared more abundant at the cell surface compared to KCNE1, which exhibited greater co-localization with the ER-marker calnexin. Examination of the extracellular culture media showed that a significant amount of KCNE2 was extracellular (both soluble and membrane-vesicle-associated). Taken together, these results suggest that during biogenesis of channels HERG is more likely to assemble with KCNE1 than KCNE2 due to distinctly different trafficking rates and retention in the cell rather than differences in relative affinity. The final channel subunit constitution, in vivo, is likely to be determined by a combination of relative cell-to-cell expression rates and differential protein processing and trafficking.
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影响因子：
10.8
作者：
Bendahhou, S;Marionneau, C;Barhanin, J
通讯作者：
Barhanin, J
影响因子：
16.2
作者：
Chen, HJ;Kim, LA;Goldstein, SAN
通讯作者：
Goldstein, SAN
DOI：
10.1152/ajpheart.00622.2001
发表时间：
2002-07-01
影响因子：
4.8
作者：
Finley, MR;Li, Y;Freeman, LC
通讯作者：
Freeman, LC
影响因子：
4.8
作者：
Lewis, A;McCrossan, ZA;Abbott, GW
通讯作者：
Abbott, GW
DOI：
10.1083/jcb.109.1.61
发表时间：
1989-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Doms RW;Russ G;Yewdell JW
通讯作者：
Yewdell JW