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EMBO reports 4, 1, 76–81 (2003)
doi:10.1038/sj.embor.embor715
Published online: January 2003
A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly
Michael Schwake1, 3, Thomas J. Jentsch1 & Thomas Friedrich2
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1 Centre for Molecular Neurobiology Hamburg, ZMNH, Falkenried 94, D-20251 Hamburg, Germany
2 Max Planck Institute of Biophysics, Kennedyallee 70, D-60596 Frankfurt, Germany
3 Present address: Institute of Biochemistry, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany
To whom correspondence should be addressed
Thomas Friedrich Tel: +49 69 6303316; Fax: +49 69 6303305; tomfritz@mpibp-frankfurt.mpg.de
Received 16 April 2002; Accepted 7 November 2002.
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Abstract
Mutations in KCNQ K+ channel genes underlie several human pathologies. KCNQ  -subunits form either homotetramers or hetero-oligomers with a restricted subset of other KCNQ -subunits or with KCNE  -subunits. KCNQ1 assembles with KCNE -subunits but not with other KCNQ -subunits. By contrast, KCNQ3 interacts with KCNQ2, KCNQ4 and KCNQ5. Using a chimaeric strategy, we show that a cytoplasmic carboxy-terminal subunit interaction domain (sid) suffices to transfer assembly properties between KCNQ3 and KCNQ1. A chimaera (KCNQ1-sidQ3) carrying the si domain of KCNQ3 within the KCNQ1 backbone interacted with KCNQ2, KCNQ3 and KCNQ4 but not with KCNQ1. This interaction was shown by enhancement of KCNQ2 currents, testing for dominant-negative effects of pore mutants, determining its effects on surface expression and co-immunoprecipitation experiments. Conversely, a KCNQ3-sidQ1 chimaera no longer affects KCNQ2 but interacts with KCNQ1. We conclude that the si domain suffices to determine the subunit specificity of KCNQ channel assembly.
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