Kvβ Subunit Oxidoreductase Activity and Kv1 Potassium Channel Trafficking

摘要: Voltage-gated Kv1 potassium channels consist of pore-forming α subunits and cytoplasmic Kvβ subunits. The latter play diverse roles in modulating the gating, stability, trafficking channels. crystallographic structure Kvβ2 subunit revealed surprising structural homology with aldo-keto reductases, including a triosephosphate isomerase barrel structure, conservation key catalytic residues, bound NADP+ cofactor (Gulbis, J. M., Mann, S., MacKinnon, R. (1999) Cell 90, 943–952). Each Kv1-associated (Kvβ1.1, Kvβ1.2, Kvβ2, Kvβ3) shares striking amino acid binding residues. Here, by combination modeling biochemical cell biological analyses structure-based mutations, we investigate potential role for putative enzymatic activity We found that all promote surface expression coexpressed Kv1.2 transfected COS-1 cells. Kvβ1.1 point mutants lacking tyrosine residue active site reductases have wild-type characteristics. However, mutations residues within pocket eliminated effects on trafficking. In cultured hippocampal neurons, coexpression led to axonal targeting Kv1.2, recapitulating localization observed many brain neurons. Similar results cells, reduced whereas those did not. Together, these data suggest and/or integrity but not activity, is required intracellular channel complexes mammalian cells