Stimulation of HERG channel activity by β-catenin.
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.
Department of Physiology, University of Tübingen, Tübingen, Germany.
Carlos
C
Munoz
Ambrish
A
Saxena
Tatsiana
T
Pakladok
Evgenii
E
Bogatikov
Jan
J
Wilmes
Guiscard
G
Seebohm
Michael
M
Föller
Florian
F
Lang
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003609:Dactinomycin / Q000494:pharmacology; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009865:Oocytes / Q000166:cytology; D018408:Patch-Clamp Techniques; D014981:Xenopus; D051176:beta Catenin / Q000378:metabolism*
D015820:Cadherins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051176:beta Catenin; D003609:Dactinomycin