Trafficking of the IKs -complex in MDCK cells: site of subunit assembly and determinants of polarized localization

Traffic. 2013 Apr;14(4):399-411. doi: 10.1111/tra.12042. Epub 2013 Feb 13.


The voltage-gated potassium channel KV 7.1 is regulated by non-pore forming regulatory KCNE β-subunits. Together with KCNE1, it forms the slowly activating delayed rectifier potassium current IKs . However, where the subunits assemble and which of the subunits determines localization of the IKs -complex has not been unequivocally resolved yet. We employed trafficking-deficient KV 7.1 and KCNE1 mutants to investigate IKs trafficking using the polarized Madin-Darby Canine Kidney cell line. We find that the assembly happens early in the secretory pathway but provide three lines of evidence that it takes place in a post-endoplasmic reticulum compartment. We demonstrate that KV 7.1 targets the IKs -complex to the basolateral membrane, but that KCNE1 can redirect the complex to the apical membrane upon mutation of critical KV 7.1 basolateral targeting signals. Our data provide a possible explanation to the fact that KV 7.1 can be localized apically or basolaterally in different epithelial tissues and offer a solution to divergent literature results regarding the effect of KCNE subunits on the subcellular localization of KV 7.1/KCNE complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Dogs
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / metabolism
  • KCNQ1 Potassium Channel / chemistry
  • KCNQ1 Potassium Channel / genetics
  • KCNQ1 Potassium Channel / metabolism*
  • Madin Darby Canine Kidney Cells
  • Mutation, Missense
  • Potassium Channels, Voltage-Gated / chemistry
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • Protein Interaction Domains and Motifs
  • Protein Multimerization*
  • Protein Sorting Signals / genetics
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Protein Transport
  • Secretory Pathway


  • KCNE1 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Potassium Channels, Voltage-Gated
  • Protein Sorting Signals
  • Protein Subunits