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Do sodium channel proteolytic fragments regulate sodium channel expression?

Onwuli, Donatus O.; Yañez-Bisbe, Laia; Pinsach-Abuin, Mel·lina; Tarradas, Anna; Brugada, Ramon; Greenman, John; Pagans, Sara; Beltran-Alvarez, Pedro

Authors

Donatus O. Onwuli

Laia Yañez-Bisbe

Mel·lina Pinsach-Abuin

Anna Tarradas

Ramon Brugada

Sara Pagans



Abstract

© 2017 Taylor & Francis The cardiac voltage-gated sodium channel (gene: SCN5A, protein: Na V 1.5) is responsible for the sodium current that initiates the cardiomyocyte action potential. Research into the mechanisms of SCN5A gene expression has gained momentum over the last few years. We have recently described the transcriptional regulation of SCN5A by GATA4 transcription factor. In this addendum to our study, we report our observations that 1) the linker between domains I and II (L DI-DII ) of Na V 1.5 contains a nuclear localization signal (residues 474–481) that is necessary to localize L DI-DII into the nucleus, and 2) nuclear L DI-DII activates the SCN5A promoter in gene reporter assays using cardiac-like H9c2 cells. Given that voltage-gated sodium channels are known targets of proteases such as calpain, we speculate that Na V 1.5 degradation is signaled to the cell transcriptional machinery via nuclear localization of L DI-DII and subsequent stimulation of the SCN5A promoter.

Journal Article Type Article
Publication Date Sep 3, 2017
Journal Channels
Print ISSN 1933-6950
Electronic ISSN 1933-6969
Publisher Taylor & Francis
Peer Reviewed Peer Reviewed
Volume 11
Issue 5
Pages 476-481
Institution Citation Onwuli, D. O., Yañez-Bisbe, L., Pinsach-Abuin, M., Tarradas, A., Brugada, R., Greenman, J., …Beltran-Alvarez, P. (2017). Do sodium channel proteolytic fragments regulate sodium channel expression?. Channels, 11(5), 476-481. https://doi.org/10.1080/19336950.2017.1355663
DOI https://doi.org/10.1080/19336950.2017.1355663
Keywords Voltage-gated sodium channel; Transcription factor; Gene expression; Nuclear localisation signal; Mutagenesis
Publisher URL https://www.tandfonline.com/doi/full/10.1080/19336950.2017.1355663
Related Public URLs https://hydra.hull.ac.uk/resources/hull:15164
Copyright Statement ©2018 The University of Hull

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