The Degree of N-glycosylation Affects the Trafficking and Cell Surface Expression Levels of Kv1.4 Potassium Channels

Itaru Watanabe, Jing Zhu, Esperanza Recio-Pinto, William B. Thornhill

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Kv1.4 potassium channels are heavily glycosylated proteins involved in shaping action potentials and in neuronal excitability and plasticity. Kv1.4 N354Q, without an N-glycan, exhibited decreased protein stability and trafficking to the cell surface (Watanabe et al. in J Biol Chem 279:8879–8885, 2004). Here we investigated whether the composition of the N-glycan affected Kv1.4 cell surface expression. Kv1.4 proteins carrying N-glycans with different compositions were generated by adding glycosidase inhibitors or using N-glycosylation-deficient mutant cell lines. We found that oligomannose-type, hybrid-type, or incomplete complex-type N-glycans had a negative effect on surface protein expression of Kv1.4 compared with complex-type N-glycans. The decrease in surface protein level of Kv1.4 was mainly due to a reduction in total protein level, induced by altered N-glycan composition. Kv1.4 in CSTP-treated cells carried a unique oligomannose-type N-glycan that contains three glucose residues. This N-glycan had the most negative effect on cell surface expression of Kv1.4. It decreased Kv1.4 surface protein level by a combined mechanism of reducing total protein level and increasing ER-retention. Our data suggest that composition of the N-glycan plays an important role in protein stability and trafficking, and a sialylated complex-type N-glycan promoted high cell surface expression of Kv1.4.

Original languageEnglish (US)
Pages (from-to)187-196
Number of pages10
JournalJournal of Membrane Biology
Volume248
Issue number2
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Keywords

  • Cell surface expression
  • N-glycosylation
  • Potassium channel
  • Trafficking

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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