title: Trafficking of the IKs -complex in MDCK cells: site of subunit assembly and determinants of polarized localization.
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.
authors: The Ion Channel Group, Danish National Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
authors: Jens-Peter
authors: JP
authors: David
authors: Martin N
authors: MN
authors: Andersen
authors: Søren-Peter
authors: SP
authors: Olesen
authors: Hanne B
authors: HB
authors: Rasmussen
authors: Nicole
authors: N
authors: Schmitt
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D051657:KCNQ1 Potassium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D020125:Mutation, Missense; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D021382:Protein Sorting Signals / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D055571:Secretory Pathway
chemical_list: C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated; D021382:Protein Sorting Signals; D021122:Protein Subunits