KCNQ1/KCNE1 assembly, co-translation not required.

Vanoye CG, Welch RC, Tian C, Sanders CR, George AL
Channels (Austin). 2010 4 (2): 108-14

PMID: 20139709 · PMCID: PMC3045044 · DOI:10.4161/chan.4.2.11141

Voltage-gated potassium channels are often assembled with accessory proteins that increase their functional diversity. KCNE proteins are small accessory proteins that modulate voltage-gated potassium (K(V)) channels. Although the functional effects of various KCNE proteins have been described, many questions remain regarding their assembly with the pore-forming subunits. For example, while previous experiments with some K(V) channels suggest that the association of the pore-subunit with the accessory subunits occurs co-translationally in the endoplasmic reticulum, it is not known whether KCNQ1 assembly with KCNE1 occurs in a similar manner to generate the medically important cardiac slow delayed rectifier current (I(Ks)). In this study we used a novel approach to demonstrate that purified recombinant human KCNE1 protein (prKCNE1) modulates KCNQ1 channels heterologously expressed in Xenopus oocytes resulting in generation of I(Ks). Incubation of KCNQ1-expressing oocytes with cycloheximide did not prevent I(Ks) expression following prKCNE1 injection. By contrast, incubation with brefeldin A prevented KCNQ1 modulation by prKCNE1. Moreover, injection of the trafficking-deficient KCNE1-L51H reduced KCNQ1 currents. Together, these observations indicate that while assembly of KCNE1 with KCNQ1 does not require co-translation, functional KCNQ1-prKCNE1 channels assemble early in the secretory pathway and reach the plasma membrane via vesicular trafficking.

MeSH Terms (16)

Animals Brefeldin A Cell Membrane Cycloheximide Endoplasmic Reticulum Humans Ion Channel Gating KCNQ1 Potassium Channel Kinetics Membrane Potentials Potassium Potassium Channels, Voltage-Gated Protein Synthesis Inhibitors Protein Transport Recombinant Proteins Xenopus laevis

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