Department of Physiology, University of Tübingen, Tübingen, Germany.
PLoS One. 2012;7(8):e43353. doi: 10.1371/journal.pone.0043353. Epub 2012 Aug 15.
The multifunctional protein ß-catenin governs as transcription factor the expression of a wide variety of genes relevant for cell proliferation and cell survival. In addition, ß-catenin is localized at the cell membrane and may influence the function of channels. The present study explored the possibility that ß-catenin participates in the regulation of the HERG K(+) channel. To this end, HERG was expressed in Xenopus oocytes with or without ß-catenin and the voltage-gated current determined utilizing the dual electrode voltage clamp. As a result, expression of ß-catenin markedly upregulated HERG channel activity, an effect not sensitive to inhibition of transcription with actinomycin D (10 µM). According to chemiluminescence, ß-catenin may increase HERG channel abundance within the oocyte cell membrane. Following inhibition of channel insertion into the cell membrane by brefeldin A (5 µM) the decay of current was similar in oocytes expressing HERG together with ß-catenin to oocytes expressing HERG alone. The experiments uncover a novel function of APC/ß-catenin, i.e. the regulation of HERG channels.
多功能蛋白β-catenin 作为转录因子调控多种与细胞增殖和细胞存活相关的基因表达。此外，β-catenin 还定位于细胞膜，并可能影响通道的功能。本研究探讨了 β-catenin 是否参与调节 HERG K(+) 通道。为此，利用双电极电压钳技术，在 Xenopus 卵母细胞中表达 HERG 并与 β-catenin 共表达，然后测定电压门控电流。结果表明，β-catenin 的表达显著上调了 HERG 通道的活性，该作用对 10 µM 的放线菌素 D（转录抑制剂）不敏感。根据化学发光，β-catenin 可能会增加卵母细胞膜中 HERG 通道的丰度。用布雷菲德菌素 A（5 µM）抑制通道插入细胞膜后，在共表达 HERG 和 β-catenin 的卵母细胞中，电流衰减与单独表达 HERG 的卵母细胞相似。这些实验揭示了 APC/β-catenin 的一个新功能，即调节 HERG 通道。
