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Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression

  • Ion channels, receptors and transporters
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Abstract

T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and contribute to the release of neurotransmitters. Enhanced T-type channel expression has been causally linked to a number of pathological conditions including peripheral painful diabetic neuropathy. Recently, it was demonstrated that asparagine-linked glycosylation not only plays an essential role in regulating cell surface expression of Cav3.2 channels, but may also support glucose-dependent potentiation of T-type currents. However, the underlying mechanisms by which N-glycosylation and glucose levels modulate the expression of T-type channels remain elusive. In the present study, we show that site-specific N-glycosylation of Cav3.2 is essential to stabilize expression of the channel at the plasma membrane. In contrast, elevated external glucose concentration appears to potentiate intracellular forward trafficking of the channel to the cell surface, resulting in an increased steady-state expression of the channel protein at the plasma membrane. Collectively, our study indicates that glucose and N-glycosylation act in concert to control the expression of Cav3.2 channels, and that alteration of these mechanisms may contribute to the altered expression of T-type channels in pathological conditions.

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Acknowledgments

We are grateful to Drs. Michael E. Daily and Steven H. Green (University of Iowa) for providing the LcK-GFP construct.

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Authors and Affiliations

  1. Institute of Organic Chemistry and Biochemistry, Ion Channels and Diseases group, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Joanna Lazniewska, Yuriy Rzhepetskyy & Norbert Weiss

  2. Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Fang-Xiong Zhang & Gerald W. Zamponi

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  1. Joanna Lazniewska
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  2. Yuriy Rzhepetskyy
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  3. Fang-Xiong Zhang
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Correspondence to Norbert Weiss.

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The authors declare that they have no conflict of interest.

Financial support

Work in the Weiss laboratory is supported by the Czech Science Foundation (grant 15-13556S), the Czech Ministry of Education Youth and Sports (grant 7AMB15FR015), and the Institute of Organic Chemistry and Biochemistry (IOCB). Y.R. and J.L. are supported by an IOCB postdoctoral fellowship.

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Lazniewska, J., Rzhepetskyy, Y., Zhang, FX. et al. Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression. Pflugers Arch - Eur J Physiol 468, 1837–1851 (2016). https://doi.org/10.1007/s00424-016-1881-y

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  • DOI: https://doi.org/10.1007/s00424-016-1881-y

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