Beta subunits promote K+ channel surface expression through effects early in biosynthesis.
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.
Shi
G
G
Department of Biochemistry and Cell Biology, State University of New York, Stony Brook 11794, USA.
Nakahira
K
K
Hammond
S
S
Rhodes
K J
KJ
Schechter
L E
LE
Trimmer
J S
JS
D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004546:Elapid Venoms / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006031:Glycosylation; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D046911:Macromolecular Substances; D051379:Mice; D015221:Potassium Channels / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D014176:Protein Biosynthesis; D051381:Rats; D014162:Transfection
D004546:Elapid Venoms; D046911:Macromolecular Substances; D015221:Potassium Channels; C020273:dendrotoxin