Journal article
Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel
The Journal of biological chemistry, Vol.293(14), pp.4981-4992
04/06/2018
DOI: 10.1074/jbc.RA117.000852
PMCID: PMC5892571
PMID: 29371400
Abstract
Voltage-gated, sodium ion–selective channels (NaV) generate electrical signals contributing to the upstroke of the action potential in animals. NaVs are also found in bacteria and are members of a larger family of tetrameric voltage-gated channels that includes CaVs, KVs, and NaVs. Prokaryotic NaVs likely emerged from a homotetrameric Ca2+-selective voltage-gated progenerator, and later developed Na+ selectivity independently. The NaV signaling complex in eukaryotes contains auxiliary proteins, termed beta (β) subunits, which are potent modulators of the expression profiles and voltage-gated properties of the NaV pore, but it is unknown whether they can functionally interact with prokaryotic NaV channels. Herein, we report that the eukaryotic NaVβ1-subunit isoform interacts with and enhances the surface expression as well as the voltage-dependent gating properties of the bacterial NaV, NaChBac in Xenopus oocytes. A phylogenetic analysis of the β-subunit gene family proteins confirms that these proteins appeared roughly 420 million years ago and that they have no clear homologues in bacterial phyla. However, a comparison between eukaryotic and bacterial NaV structures highlighted the presence of a conserved fold, which could support interactions with the β-subunit. Our electrophysiological, biochemical, structural, and bioinformatics results suggests that the prerequisites for β-subunit regulation are an evolutionarily stable and intrinsic property of some voltage-gated channels.
Details
- Title: Subtitle
- Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel
- Creators
- Steven Molinarolo - From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa 52242Sora Lee - Weill Cornell Medical College, Cornell University, New York, New York 10065Lilia Leisle - Weill Cornell Medical College, Cornell University, New York, New York 10065John D Lueck - From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa 52242Daniele Granata - Institute for Computational Molecular Science, Temple University, Philadelphia, Pennsylvania 19122Vincenzo Carnevale - Institute for Computational Molecular Science, Temple University, Philadelphia, Pennsylvania 19122Christopher A Ahern - From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.293(14), pp.4981-4992
- DOI
- 10.1074/jbc.RA117.000852
- PMID
- 29371400
- PMCID
- PMC5892571
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Grant note
- 5EIA22180002 / American Heart Association Established Investigator GM122420 / National Institutes of Health NIGMS
- Language
- English
- Date published
- 04/06/2018
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984070216402771
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