Role of glycosylation in cell surface expression and stability of HERG potassium channels

Qiuming Gong, Corey L. Anderson, Craig T. January, Zhengfeng Zhou

    Research output: Contribution to journalArticle

    106 Citations (Scopus)

    Abstract

    The human ether-à-go-go-related gene (HERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel in the heart. We previously showed that HERG channel protein is modified by N-linked glycosylation. HERG protein sequence contains two extracellular consensus sites for N-linked glycosylation (N598, N629). In this study, we used the approaches of site-directed mutagenesis and biochemical modification to inhibit N-linked glycosylation and studied the role of glycosylation in the cell surface expression and turnover of HERG channels. Our results show that N598 is the only site for N-linked glycosylation and that glycosylation is not required for the cell surface expression of functional HERG channels. In contrast, N629 is not used for glycosylation, but mutation of this site (N629Q) causes a protein trafficking defect, which results in its intracellular retention. Pulse-chase experiments show that the turnover rate of nonglycosylated HERG channel is faster than that of the glycosylated form, suggesting that N-linked glycosylation plays an important role in HERG channel stability.

    Original languageEnglish (US)
    JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
    Volume283
    Issue number1 52-1
    StatePublished - 2002

    Fingerprint

    Potassium Channels
    Glycosylation
    Ether
    Genes
    Delayed Rectifier Potassium Channels
    Protein Transport
    Site-Directed Mutagenesis
    Proteins
    Mutation

    Keywords

    • Arrhythmia
    • Heart
    • Ion channels
    • Mutations
    • Patch clamp

    ASJC Scopus subject areas

    • Physiology

    Cite this

    Role of glycosylation in cell surface expression and stability of HERG potassium channels. / Gong, Qiuming; Anderson, Corey L.; January, Craig T.; Zhou, Zhengfeng.

    In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 1 52-1, 2002.

    Research output: Contribution to journalArticle

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    AU - January, Craig T.

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