| 20139709 |
Vanoye CG, Welch RC, Tian C, Sanders CR, George AL Jr: KCNQ1/KCNE1 assembly, co-translation not required. Channels. 2010 Mar 6;4(2).
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. |
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