Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif.
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.
Department of Medical Physiology and Copenhagen Heart Research Center, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
Thomas
T
Jespersen
Hanne B
HB
Rasmussen
Morten
M
Grunnet
Henrik S
HS
Jensen
Kamilla
K
Angelo
Delphine S
DS
Dupuis
Lotte K
LK
Vogel
Nanna K
NK
Jorgensen
Dan A
DA
Klaerke
Søren-Peter
SP
Olesen
D020816:Amino Acid Motifs / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D004285:Dogs; D004594:Electrophysiology / Q000379:methods; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism
D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D014443:Tyrosine