S-acylation regulates Kv1.5 channel surface expression.
S-acylation regulates Kv1.5 channel surface expression.
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S-酰化调节 Kv1.5 通道表面表达。
DOI：
10.1152/ajpcell.00480.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Martens,JeffreyR
中科院分区：
文献类型：
--
作者：
Zhang,Lian;Foster,Karyn;Li,Qiuju;Martens,JeffreyR
The number of ion channels expressed on the cell surface shapes the complex electrical response of excitable cells. An imbalance in the ratio of inward and outward conducting channels is unfavorable and often detrimental. For example, over- or underexpression of voltage-gated K+(Kv) channels can be cytotoxic and in some cases lead to disease. In this study, we demonstrated a novel role forS-acylation in Kv1.5 cell surface expression. In transfected fibroblasts, biochemical evidence showed that Kv1.5 is posttranslationally modified on both the NH2and COOH termini via hydroxylamine-sensitive thioester bonds. Pharmacological inhibition ofS-acylation, but not myristoylation, significantly decreased Kv1.5 expression and resulted in accumulation of channel protein in intracellular compartments and targeting for degradation. Channel protein degradation was rescued by treatment with proteasome inhibitors. Time course experiments revealed thatS-acylation occurred in the biosynthetic pathway of nascent channel protein and showed that newly synthesized Kv1.5 protein, but not protein expressed on the cell surface, is sensitive to inhibitors of thioacylation. Sensitivity to inhibitors ofS-acylation was governed by COOH-terminal, but not NH2-terminal, cysteines. Surprisingly, although intracellular cysteines were required forS-acylation, mutation of these residues resulted in an increase in Kv1.5 cell surface channel expression, suggesting that screening of free cysteines by fatty acylation is an important regulatory step in the quality control pathway. Together, these results show thatS-acylation can regulate steady-state expression of Kv1.5.
