An endoplasmic reticulum trafficking signal prevents surface expression of a voltage- and Ca2+-activated K+ channel splice variant.
An endoplasmic reticulum trafficking signal prevents surface expression of a voltage- and Ca2+-activated K+ channel splice variant.
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DOI：
10.1073/pnas.0302919101
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发表时间：
2004-07
影响因子：
11.1
通讯作者：
M. M. Zarei-M.;M. Eghbali;A. Alioua;M. Song;Hans-Günther Knaus;Enrico Stefani;L. Toro
中科院分区：
文献类型：
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作者：
M. M. Zarei-M.;M. Eghbali;A. Alioua;M. Song;Hans-Günther Knaus;Enrico Stefani;L. Toro
在细胞运输机制的不同阶段，蛋白质递送到受限的质膜结构域受到精细的调节。交通控制涉及内质网/高尔基复合体对输出/保留/检索信号的识别，这将决定蛋白质的命运。电压和Ca（2+）激活的K（+）通道α亚基的剪接变体（SV） SV1在内质网中积累通道，阻止其表面表达。我们发现SV1插入物包含一个非碱性、疏水的保留/检索基序CVLF，它不会干扰SV1的正常折叠和四聚化。CVLF对内质网蛋白的定位与它的位置无关；最初，在第一个内部环上，SV1插入物或CVLF如果放置在α -亚基胞内羧基末端的中间或末端，其表现同样良好。此外，CVLF能够限制独立表达的跨膜蛋白β 1亚基的交通。CVLF存在于不同物种和低等生物的蛋白质中。因此，CVLF可能已经进化为细胞流量的调节器。
Protein delivery to restricted plasma membrane domains is exquisitely regulated at different stages of the cell trafficking machinery. Traffic control involves the recognition of export/retention/retrieval signals in the endoplasmic reticulum (ER)/Golgi complex that will determine protein fate. A splice variant (SV), SV1, of the voltage- and Ca(2+)-activated K(+) channel alpha-subunit accumulates the channel in the ER, preventing its surface expression. We show that SV1 insert contains a nonbasic, hydrophobic retention/retrieval motif, CVLF, that does not interfere with proper folding and tetramerization of SV1. Localization of proteins in the ER by CVLF is independent of its position; originally, on the first internal loop, SV1 insert or CVLF perform equally well if placed at the middle or end of the alpha-subunit intracellular carboxyl terminus. Also, CVLF is able to restrict the traffic of an independently expressed transmembrane protein, beta 1-subunit. CVLF is present in proteins across species and in lower organisms. Thus, CVLF may have evolved to serve as a regulator of cellular traffic.