Trafficking of the IKs -Complex in MDCK Cells: Site of Subunit Assembly and Determinants of Polarized Localization

TY - JOUR

T1 - Trafficking of the IKs -Complex in MDCK Cells

T2 - Site of Subunit Assembly and Determinants of Polarized Localization

AU - David, Jens-Peter

AU - Andersen, Martin N

AU - Olesen, Søren-Peter

AU - Rasmussen, Hanne B

AU - Schmitt, Nicole

N1 - © 2013 John Wiley & Sons A/S.

PY - 2013/4

Y1 - 2013/4

N2 - The voltage-gated potassium channel KV7.1 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 KV7.1 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 KV7.1 targets the IKs-complex to the basolateral membrane, but that KCNE1 can redirect the complex to the apical membrane upon mutation of critical KV7.1 basolateral targeting signals. Our data provide a possible explanation to the fact that KV7.1 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 KV7.1/KCNE complexes.

AB - The voltage-gated potassium channel KV7.1 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 KV7.1 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 KV7.1 targets the IKs-complex to the basolateral membrane, but that KCNE1 can redirect the complex to the apical membrane upon mutation of critical KV7.1 basolateral targeting signals. Our data provide a possible explanation to the fact that KV7.1 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 KV7.1/KCNE complexes.

U2 - 10.1111/tra.12042

DO - 10.1111/tra.12042

M3 - Journal article

C2 - 23324056

SN - 1398-9219

VL - 14

SP - 399

EP - 411

JO - Traffic

JF - Traffic

IS - 4

ER -