BETA-SUBUNITS PROMOTE K+ CHANNEL SURFACE EXPRESSION THROUGH EFFECTS EARLY IN BIOSYNTHESIS

Voltage-gated K+ channels are protein complexes composed of ion-conduc ting integral membrane alpha subunits and cytoplasmic beta subunits. H ere, we show that, in transfected mammalian cells, the predominant bet a subunit isoform in brain, Kv beta 2, associates with the Kv1.2 alpha subunit early in channel biosynthesis and that KvPP exerts multiple c haperone-like effects on associated Kv1.2 including promotion of cotra nslational N-linked glycosylation of the nascent Kv1.2 polypeptide, in creased stability of Kv beta 2/Kv1.2 complexes, and increased efficien cy of cell surface expression of Kv1.2. Taken together, these results indicate that while some cytoplasmic K+ channel beta subunits affect t he inactivation kinetics of alpha subunits, a more general, and perhap s more fundamental, role is to mediate the biosynthetic maturation and surface expression of voltage-gated K+ channel complexes. These findi ngs provide a molecular basis for recent genetic studies indicating th at beta subunits are key determinants of neuronal excitability.