KCNE1 subunits require co-assembly with K+ channels for efficient trafficking and cell surface expression
KCNE1 subunits require co-assembly with K+ channels for efficient trafficking and cell surface expression
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DOI：
10.1074/jbc.m604398200
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发表时间：
2006-12-29
影响因子：
4.8
通讯作者：
Kobertz, William R.
中科院分区：
文献类型：
--
作者：
Chandrasekhar, Kshama D.;Bas, Tuba;Kobertz, William R.
KCNE肽是一类I型跨膜β亚基，与各种电压门控K+通道组装并调节其门控和离子传导特性。因此，破坏KCNE-K+通道复合物的组装和运输的突变会引起疾病。负责确保KCNE肽与电压门控K+通道组装的细胞机制尚未阐明。通过酶解糖基化、免疫荧光和定量细胞表面标记实验，我们发现KCNE1肽保留在分泌途径的早期阶段，直到它们与特定的K+通道亚基共同组装；共组装通过分泌途径介导KCNE1的进展并导致细胞表面表达。我们还解决了我们的结果与先前在人胚胎肾细胞中的研究之间的明显差异，该研究表明野生型KCNE1肽可以在没有外源性表达K+通道亚基的情况下到达质膜。通过比较三种细胞系中的KCNE1转运，我们的数据表明，在人类胚胎肾细胞中观察到的KCNE1转运错误可能部分是由于这些细胞中存在内源性电压门控K+通道。
KCNE peptides are a class of type I transmembrane beta subunits that assemble with and modulate the gating and ion conducting properties of a variety of voltage-gated K+ channels. Accordingly, mutations that disrupt the assembly and trafficking of KCNE-K+ channel complexes give rise to disease. The cellular mechanisms responsible for ensuring that KCNE peptides assemble with voltage-gated K+ channels have yet to be elucidated. Using enzymatic deglycosylation, immunofluorescence, and quantitative cell surface labeling experiments, we show that KCNE1 peptides are retained in the early stages of the secretory pathway until they co-assemble with specific K+ channel subunits; co-assembly mediates KCNE1 progression through the secretory pathway and results in cell surface expression. We also address an apparent discrepancy between our results and a previous study in human embryonic kidney cells, which showed wild type KCNE1 peptides can reach the plasma membrane without exogenously expressed K+ channel subunits. By comparing KCNE1 trafficking in three cell lines, our data suggest that the errant KCNE1 trafficking observed in human embryonic kidney cells may be due, in part, to the presence of endogenous voltage-gated K+ channels in these cells.