Kv1.4 and Kv1.1 potassium channel homomers have been shown to exhibit different intracellular trafficking programmes and cell-surface expression levels in cell lines: a determinant in the pore region of Kv1.4 and Kv1.1 [Zhu, Watanabe, Gomez and Thornhill (2001) J. Biol. Chem. 276, 39419–39427] and a cytoplasmic C-terminal VXXSL determinant on Kv1.4 [Li, Takimoto and Levitan (2000) J. Biol. Chem. 275, 11597–11602] have been described, which affected trafficking and cell-surface expression levels. In the present study, we examined whether trafficking pore determinants influenced any cytoplasmic C-terminal trafficking determinant. We found that removal of VXXSL from a Kv1.4 chimaera that contained the pore of Kv1.1 did not affect cell-surface trafficking. Therefore removal of the C-terminal VXXSL of Kv1.4 inhibited protein surface levels only in the presence of the Kv1.4 pore. In contrast, truncating the cytoplasmic C-terminus of Kv1.1 or truncating a Kv1.1 chimaera with the pore of Kv1.4, had little effect on surface protein levels. Furthermore, the subregion of the Kv1.4 pore trafficking determinant that was required for the inhibitory effect of VXXSL removal was mapped to a threonine residue in the deep pore region. Therefore the Kv1.4 pore determinant affected the trafficking and cell-surface levels directed by the C-terminal VXXSL determinant. Different Kv1 trafficking programmes would affect cell-surface expression levels either positively or negatively and also cell signalling. Cells may use differential trafficking programmes of membrane proteins as a post-translational mechanism to regulate surface protein levels and cell function.
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November 2003
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Research Article|
November 01 2003
Trafficking of Kv1.4 potassium channels: interdependence of a pore region determinant and a cytoplasmic C-terminal VXXSL determinant in regulating cell-surface trafficking
Jing ZHU;
Jing ZHU
Department of Biological Sciences, Fordham University, Bronx, NY 10458, U.S.A.
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Itaru WATANABE;
Itaru WATANABE
Department of Biological Sciences, Fordham University, Bronx, NY 10458, U.S.A.
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Barbara GOMEZ;
Barbara GOMEZ
Department of Biological Sciences, Fordham University, Bronx, NY 10458, U.S.A.
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William B. THORNHILL
William B. THORNHILL
1
Department of Biological Sciences, Fordham University, Bronx, NY 10458, U.S.A.
1To whom correspondence should be addressed (e-mail thornhill@fordham.edu).
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Publisher: Portland Press Ltd
Received:
June 14 2003
Revision Received:
July 24 2003
Accepted:
August 06 2003
Accepted Manuscript online:
August 06 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 375 (3): 761–768.
Article history
Received:
June 14 2003
Revision Received:
July 24 2003
Accepted:
August 06 2003
Accepted Manuscript online:
August 06 2003
Citation
Jing ZHU, Itaru WATANABE, Barbara GOMEZ, William B. THORNHILL; Trafficking of Kv1.4 potassium channels: interdependence of a pore region determinant and a cytoplasmic C-terminal VXXSL determinant in regulating cell-surface trafficking. Biochem J 1 November 2003; 375 (3): 761–768. doi: https://doi.org/10.1042/bj20030885
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