Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif.

TY - JOUR

T1 - Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif.

AU - Jespersen, Thomas

AU - Rasmussen, Hanne B

AU - Grunnet, Morten

AU - Jensen, Henrik S.

AU - Angelo, Kamilla

AU - Dupuis, Delphine S

AU - Vogel, Lotte K

AU - Jorgensen, Nanna K

AU - Klaerke, Dan A

AU - Olesen, Søren-Peter

N1 - Keywords: Amino Acid Motifs; Amino Acid Sequence; Animals; Cell Membrane; Cell Polarity; Cells, Cultured; Dogs; Electrophysiology; KCNQ Potassium Channels; KCNQ1 Potassium Channel; Molecular Sequence Data; Mutation; Oocytes; Potassium Channels, Voltage-Gated; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor; Tyrosine; Xenopus

PY - 2004

Y1 - 2004

N2 - KCNQ1 potassium channels are expressed in many epithelial tissues as well as in the heart. In epithelia KCNQ1 channels play an important role in salt and water transport and the channel has been reported to be located apically in some cell types and basolaterally in others. Here we show that KCNQ1 channels are located basolaterally when expressed in polarised MDCK cells. The basolateral localisation of KCNQ1 is not affected by co-expression of any of the five KCNE beta-subunits. We characterise two independent basolateral sorting signals present in the N-terminal tail of KCNQ1. Mutation of the tyrosine residue at position 51 resulted in a non-polarized steady-state distribution of the channel. The importance of tyrosine 51 in basolateral localisation was emphasized by the fact that a short peptide comprising this tyrosine was able to redirect the p75 neurotrophin receptor, an otherwise apically located protein, to the basolateral plasma membrane. Furthermore, a di-leucine-like motif at residues 38-40 (LEL) was found to affect the basolateral localisation of KCNQ1. Mutation of these two leucines resulted in a primarily intracellular localisation of the channel.

AB - KCNQ1 potassium channels are expressed in many epithelial tissues as well as in the heart. In epithelia KCNQ1 channels play an important role in salt and water transport and the channel has been reported to be located apically in some cell types and basolaterally in others. Here we show that KCNQ1 channels are located basolaterally when expressed in polarised MDCK cells. The basolateral localisation of KCNQ1 is not affected by co-expression of any of the five KCNE beta-subunits. We characterise two independent basolateral sorting signals present in the N-terminal tail of KCNQ1. Mutation of the tyrosine residue at position 51 resulted in a non-polarized steady-state distribution of the channel. The importance of tyrosine 51 in basolateral localisation was emphasized by the fact that a short peptide comprising this tyrosine was able to redirect the p75 neurotrophin receptor, an otherwise apically located protein, to the basolateral plasma membrane. Furthermore, a di-leucine-like motif at residues 38-40 (LEL) was found to affect the basolateral localisation of KCNQ1. Mutation of these two leucines resulted in a primarily intracellular localisation of the channel.

U2 - 10.1242/jcs.01318

DO - 10.1242/jcs.01318

M3 - Journal article

C2 - 15316073

SN - 0021-9533

VL - 117

SP - 4517

EP - 4526

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - Pt 19

ER -