Stimulation of HERG Channel Activity by β-cateninReportar como inadecuado

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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.

Autor: Carlos Munoz, Ambrish Saxena, Tatsiana Pakladok, Evgenii Bogatikov, Jan Wilmes, Guiscard Seebohm, Michael Föller, Florian Lang



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