β Subunits promote K+ channel surface expression through effects early in biosynthesis

Gongyi Shi, Kensuke Nakahira, Scott Hammond, Kenneth J. Rhodes, Lee E. Schechter, James Trimmer

Research output: Contribution to journalArticlepeer-review

327 Scopus citations

Abstract

Voltage-gated K+ channels are protein complexes composed of ion- conducting integral membrane subunits and cytoplasmic β subunits. Here, we show that, in transfected mammalian cells, the predominant β subunit isoform in brain, Kvβ2, associates with the Kv1.2 α subunit early in channel biosynthesis and that Kvβ2 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 Kvβ2/Kv1.2 complexes, and increased efficiency of cell surface expression of Kv1.2. Taken together, these results indicate that while some cytoplasmic K+ channel β subunits affect the inactivation kinetics of α 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 β subunits are key determinants of neuronal excitability.

Original languageEnglish (US)
Pages (from-to)843-852
Number of pages10
JournalNeuron
Volume16
Issue number4
DOIs
StatePublished - Apr 1996
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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