Differential association between HERG and KCNE1 or KCNE2

Sung Yon Um, Thomas V. McDonald

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The small proteins encoded by KCNE1 and KCNE2 have both been proposed as accessory subunits for the HERG channel. Here we report our investigation into the cell biology of the KCNE-HERG interaction. In a co-expression system, KCNE1 was more readily co-precipitated with co-expressed HERG than was KCNE2. When forward protein trafficking was prevented (either by Brefeldin A or engineering an ER-retention/ retrieval signal onto KCNE cDNA) the Intracellular abundance of KCNE2 and its association with HERG markedly increased relative to KCNE1. HERG co-localized more completely with KCNE1 than with KCNE2 in all the membrane-processing compartments of the cell (ER, Golgi and plasma membrane). By surface labeling and confocal immunofluorescence, KCNE2 appeared more abundant at the cell surface compared to KCNE1, which exhibited greater colocalization with the ER-marker calnexin. Examination of the extracellular culture media showed that a significant amount of KCNE2 was extracellular (both soluble and membrane-vesicle-assodated). Taken together, these results suggest that during biogenesis of channels HERG is more likely to assemble with KCNE1 than KCNE2 due to distinctly different trafficking rates and retention in the cell rather than differences in relative affinity. The final channel subunit constitution, in vivo, is likely io be determined by a combination of relative cell-to-cell expression rates and differential protein processing and trafficking.

Original languageEnglish (US)
Article numbere933
JournalPLoS One
Volume2
Issue number9
DOIs
StatePublished - Sep 26 2007

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Cell membranes
Protein Transport
Calnexin
Cytology
Membranes
Brefeldin A
Proteins
Cell Membrane
Accessories
cells
Processing
calnexin
Labeling
Culture Media
Constitution and Bylaws
brefeldin A
Complementary DNA
protein transport
Fluorescent Antibody Technique
Cell Biology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Differential association between HERG and KCNE1 or KCNE2. / Um, Sung Yon; McDonald, Thomas V.

In: PLoS One, Vol. 2, No. 9, e933, 26.09.2007.

Research output: Contribution to journalArticle

Um, Sung Yon ; McDonald, Thomas V. / Differential association between HERG and KCNE1 or KCNE2. In: PLoS One. 2007 ; Vol. 2, No. 9.
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