Premium
A carboxy‐terminal domain determines the subunit specificity of KCNQ K + channel assembly
Author(s) -
Schwake Michael,
Jentsch Thomas J,
Friedrich Thomas
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.embor715
Subject(s) - protein subunit , chimera (genetics) , immunoprecipitation , cytoplasm , hek 293 cells , potassium channel , chemistry , mutant , microbiology and biotechnology , c terminus , biology , biophysics , biochemistry , gene , amino acid
Mutations in KCNQ K + channel genes underlie several human pathologies. KCNQ α‐subunits form either homotetramers or hetero‐oligomers with a restricted subset of other KCNQ α‐subunits or with KCNE β‐subunits. KCNQ1 assembles with KCNE β‐subunits but not with other KCNQ α‐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‐ sid Q3 ) 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‐ sid Q1 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.