A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly.
Mutations in KCNQ K(+) channel genes underlie several human pathologies. KCNQ alpha-subunits form either homotetramers or hetero-oligomers with a restricted subset of other KCNQ alpha-subunits or with KCNE beta-subunits. KCNQ1 assembles with KCNE beta-subunits but not with other KCNQ alpha-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.
Schwake
Michael
M
Centre for Molecular Neurobiology Hamburg, ZMNH, Falkenried 94, Germany.
Jentsch
Thomas J
TJ
Friedrich
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009865:Oocytes; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D018076:DNA, Complementary; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; C117367:KCNQ4 protein, human; D046911:Macromolecular Substances; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins