KCNQ1/KCNE1 assembly, co-translation not required

Carlos G. Vanoye, Richard C. Welch, Changlin Tian, Charles R. Sanders, Alfred L. George

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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 (KV) channels. Although the functional effects of various KCNE proteins have been described, many questions remain regarding their assembly with the poreforming subunits. For example, while previous experiments with some KV 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 (IKs). 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 IKs. Incubation of KCNQ1-expressing oocytes with cycloheximide did not prevent IKs 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.

Original languageEnglish (US)
Pages (from-to)108-114
Number of pages7
JournalChannels
Volume4
Issue number2
DOIs
StatePublished - 2010

Keywords

  • Accessory subunit
  • Channel assembly
  • Potassium channel
  • Protein purification
  • Trafficking

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Fingerprint Dive into the research topics of 'KCNQ1/KCNE1 assembly, co-translation not required'. Together they form a unique fingerprint.

Cite this