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XB-ART-54579
J Biol Chem 2018 Apr 06;29314:4981-4992. doi: 10.1074/jbc.RA117.000852.
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Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel.

Molinarolo S , Lee S , Leisle L , Lueck JD , Granata D , Carnevale V , Ahern CA .


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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.

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References [+] :
Ahern, The hitchhiker's guide to the voltage-gated sodium channel galaxy. 2016, Pubmed