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First published online 17 August 2004
doi: 10.1242/jcs.01318

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

Thomas Jespersen^1,*, Hanne B. Rasmussen^1,*,, Morten Grunnet^1,3, Henrik S. Jensen¹, Kamilla Angelo¹, Delphine S. Dupuis¹, Lotte K. Vogel², Nanna K. Jorgensen¹, Dan A. Klaerke¹ and Søren-Peter Olesen^1,3

¹ Department of Medical Physiology and Copenhagen Heart Research Center, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
² Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
³ NeuroSearch A/S, Pederstrupvej 93, 2750 Ballerup, Denmark

Author for correspondence (e-mail: hannebr{at}mfi.ku.dk)

Accepted 18 May 2004

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 ß-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.

Key words: KCNQ1, KCNE, MDCK cells, Confocal microscopy, Subcellular distribution

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