Referenced in: none

Automatically associated channels: Slo1

Title: Trafficking of the I(Ks) -complex in MDCK cells: site of subunit assembly and determinants of polarized localization.

Authors: Jens-Peter David, Martin N Andersen, Søren-Peter Olesen, Hanne B Rasmussen, Nicole Schmitt

Journal, date & volume: Traffic, 2013 Jan 16 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23324056

Abstract
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.