1. βSubunits Promote K+ Channel Surface Expression through Effects Early in Biosynthesis
- Author
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Gongyi Shi, Lee E. Schechter, Kensuke Nakahira, Scott M. Hammond, James S. Trimmer, and Kenneth J. Rhodes
- Subjects
Gene isoform ,Glycosylation ,Potassium Channels ,Macromolecular Substances ,Neuroscience(all) ,Alpha (ethology) ,Gene Expression ,Biology ,Transfection ,Cell Line ,chemistry.chemical_compound ,Mice ,Protein biosynthesis ,Animals ,Beta (finance) ,Fluorescent Antibody Technique, Indirect ,Immunosorbent Techniques ,G alpha subunit ,Brain Chemistry ,Elapid Venoms ,General Neuroscience ,Cell Membrane ,Immunohistochemistry ,Cell biology ,Rats ,chemistry ,Cytoplasm ,Protein Biosynthesis ,biology.protein ,Cattle ,Electrophoresis, Polyacrylamide Gel ,ATP synthase alpha/beta subunits - Abstract
Voltage-gated K+ channels are protein complexes composed of ion-conducting integral membrane alpha subunits and cytoplasmic beta subunits. Here, we show that, in transfected mammalian cells, the predominant beta subunit isoform in brain, Kv beta 2, associates with the Kv1.2 alpha subunit early in channel biosynthesis and that Kv beta 2 exerts multiple chaperone-like effects on associated Kv1.2 including promotion of cotranslational N-linked glycosylation of the nascent Kv1.2 polypeptide, increased stability of Kv beta 2/Kv1.2 complexes, and increased efficiency of cell surface expression of Kv1.2. Taken together, these results indicate that while some cytoplasmic K+ channel beta subunits affect the inactivation kinetics of alpha subunits, a more general, and perhaps more fundamental, role is to mediate the biosynthetic maturation and surface expression of voltage-gated K+ channel complexes. These findings provide a molecular basis for recent genetic studies indicating that beta subunits are key determinants of neuronal excitability.
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